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Evaluation of Disintegration Testing of Different Fast Dissolving Tablets Using the Texture Analyzer
Pharmaceutical Development and Technology
Abstract
The in vitro disintegration behavior of fast dissolving systems manufactured by the main commercialized technologies was studied using the texture analyzer (TA) instrument. Quantitative parameters were employed to characterize the effect of the major test variables on the disintegration profiles. The average disintegration profiles of the products were compared using the test conditions that minimized these effects and at the same time mimicked the in vivo situation in the patient's mouth. The differences in the disintegration mechanisms of the fast dissolving systems were reflected in the shape of their disintegration profiles and in the parameters derived from the profiles. The differences were explained in relation to the technology and/or formulation characteristics involved in the manufacture of each product. The in vitro disintegration times obtained under the simulated in vivo conditions were correlated with the reported in vivo disintegration times.
... The USP "Guidance for Industry: Orally Disintegrating Tablets" has stipulated the need for an alternative test for measuring the disintegration time of ODT which bears closer resemblance with in vivo conditions 2 . Previous efforts have been made at conducting an in vivo relevant/correlating test, with methods ranging from the fabrication of tailored equipment [5][6][7][8] , to improvised methods that were developed using currently available lab equipment [9][10][11][12][13][14][15][16] . However, these different tests suffer from various limitations including absence of controlled conditions such as temperature and humidity as well as limited data for demonstrating in vitro/in vivo correlation (IVIVC). ...
... The disintegration compartment was placed under the probe of a texture analyser (Brookfield Engineering's CT3 Texture Analyser, Harlow, UK), set at speed of 2 mm/s. Once the tablet came into contact with the disintegration bed, the probe was set to apply a fixed 50 g weight for a set amount of time 12,13 . A plot of distance vs time was then generated from which disintegration time was calculated. ...
... Validation of disintegration using newly developed aston disintegration tester. Although several attempts have been made to design a test that is more specific to ODTs [5][6][7]9,10,[12][13][14][15][16][19][20][21][22][23][24][25][26] , no test has reached approval specifically for ODT disintegration testing. The Aston test was conceptualised and developed as there is currently no validated test that broadly mimics the oral in vivo conditions encountered by an ODT during disintegration. ...
Disintegration time is the key critical quality attribute for a tablet classed as an Orally Disintegrating Tablet (ODT). The currently accepted in vitro testing regimen for ODTs is the standard United States Pharmacopeia (USP) test for disintegration of immediate release tablets, which requires a large volume along with repeated submergence of the dosage form within the disintegration medium. The aim of this study was to develop an in vivo relevant ODT disintegration test that mimicked the environment of the oral cavity, including lower volume of disintegration medium, with relevant temperature and humidity that represent the conditions of the mouth. The results showed that the newly developed Aston test was able to differentiate between different ODTs with small disintegration time windows, as well as between immediate release tablets and ODTs. The Aston test provided higher correlations between ODT properties and disintegration time compared to the USP test method and most significantly, resulted in a linear in vitro/in vivo correlation (IVIVC) (R2 value of 0.98) compared with a “hockey stick” profile of the USP test. This study therefore concluded that the newly developed Aston test is an accurate, repeatable, relevant and robust test method for assessing ODT disintegration time which will provide the pharmaceutical industry and regulatory authorities across the world with a pragmatic ODT testing regime.
... As the measurement started, the TA probe moved downwards until the probe with the tablet had reached the bottom of the beaker. At this point, the TA applied a force of 50 g (25) to the tablet and recorded the immersion depth of the probe into the tablet. The analysis of the immersion depth/distance over time plots was done according to the method described by Dor et al. (24) and el-Arini et al. (25). ...
... At this point, the TA applied a force of 50 g (25) to the tablet and recorded the immersion depth of the probe into the tablet. The analysis of the immersion depth/distance over time plots was done according to the method described by Dor et al. (24) and el-Arini et al. (25). The obtained curves show three characteristic regions: ...
... The TA measurements revealed that there are remarkable differences between the three methods investigated with respect to the disintegration time. The first method described by Dor et al. (24) and el-Arini et al. (25), where the tablet was attached flat to the probe head, resulted in the longest disintegration times, even for formulations showing fast disintegration in the beaker. By employing this experimental setup, the upper circular area of the tablet is attached to the probe head, while the lower circular area is pressed against the bottom of the beaker. ...
Purpose
The design of pediatric formulations is challenging. Solid dosage forms for children have to meet the needs of different ages, e.g. high number of dosing increments and strengths. A modular formulation strategy offering the possibility of rapid prototyping was applied. Different tablet compositions and the resulting tablet characteristics were investigated for dispersible tablets using customized analytical methods.
Methods
Fluid bed granules were blended with extragranular components, and compressed to tablets. Disintegration behavior was studied with a Texture Analyzer and a Tensiometer.
Results
Methods for determination of disintegration time and water uptake of tablets were developed with a Texture Analyzer, and a Tensiometer, respectively. Twenty-two different tablet formulations were prepared and analyzed with respect to disintegration time, hardness, friability, and viscosity. Multivariate data analysis revealed a high impact of type and amount of viscosity enhancer on the disintegration behavior of tablets. An optimized formulation was selected with a disintegration time of 24 s.
Conclusion
Methods providing additional information on the disintegration behavior of dispersible tablets compared to standard pharmacopoeia methods were established. Selecting the right type and level of viscosity enhancer and superdisintegrant was critical for developing pediatric tablets with a disintegration time of less than 30 s but still pleasant mouth feel.
... Disintegration Test using Texture Analyzer [27,28] In another study, a texture analysis apparatus was used to measure the start and end time points of tablet disintegration [27]. The set up is shown in Fig. 4. A constant penetration force was applied to tablets via a cylindrical flat-ended probe. ...
... Disintegration Test using Texture Analyzer [27,28] In another study, a texture analysis apparatus was used to measure the start and end time points of tablet disintegration [27]. The set up is shown in Fig. 4. A constant penetration force was applied to tablets via a cylindrical flat-ended probe. ...
... Texture analyzer apparatus for disintegration test (from reference [27]) ...
Mouth dissolving tablets are well established dosage forms available in the market. The numerous advantages that they offer to the patients in terms of compliance as well as to the manufacturers in terms of huge revenues by line extension of products are well known. In spite of such popularity, there seems to be lack of a standardized system to characterize these dosage forms. Enormous work has been done in this field, wherein some of the researchers have developed their own methods of evaluation. This article attempts to present a detailed review regarding technological advances made so far in the area of evaluation of mouth dissolving tablets with respect to special characteristics of these unique dosage forms. In the absence of any available standardized method, the author’s recommendation on critical issues in the field may be considered.
... The distance-time curves were regarded as disintegration profiles, as they allowed the detection of the onset and endpoint of disintegration (Dor and Fix, 2000). Further studies proposed maintaining the applied force for a predetermined time and placing the disintegration media, water, or simulated saliva, in a thermostated bath (Abdelbary et al., 2005;El-Arini and Clas, 2002). When investigating the media volume effect, it appeared that a volume increase from 1 to 3 ml determined faster disintegration onset and higher disintegration rate, but beyond 2 ml, no significant influence of the volume was shown. ...
... They compared the Pharmacopoeial tests with two TA-adapted tests reported in the literature and revealed that the texture approach was more appropriate for OL testing. First, they applied the El-Arini and Clas test developed for ODTs (El-Arini and Clas, 2002), which was unable to accurately evaluate the quick disintegration of OLs, and afterwards the Abdelbary test (Abdelbary et al., 2005), which was found suitable for OL testing and led to high result reproducibility . ...
In the past few decades, texture analysis (TA) has gained importance as a valuable method for the characterization of solid oral dosage forms. As a result, an increasing number of scientific publications describe the textural methods that evaluate the extremely diverse category of solid pharmaceutical products. Within the current work, the use of texture analysis in the characterization of solid oral dosage forms is summarised with a focus on the evaluation of intermediate and finished oral pharmaceutical products. Several texture methods are reviewed regarding the applications in mechanical characterization, and mucoadhesion testing, but also in estimating the disintegration time and in vivo specific features of oral dosage forms. As there are no pharmacopoeial standards for pharmaceutical products tested through texture analysis, and there are important differences between reported results due to different experimental conditions, the choice of testing protocol and parameters is challenging. Thereby, this work aims to guide the research scientists and quality assurance professionals involved in different stages of drug development into the selection of optimal texture methodologies depending on the product characteristics and quality control needs.
... Over the years many researchers have reported on swelling and disintegration tests of tablets by various techniques. These include texture analyser (TA), 15 magnetic resonance imaging (MRI), 16 terahertz time-domain spectroscopy (THz-TDS) 17 etc. El-Arini and Clas 15 have studied the in vitro disintegration of fast-dissolving tablets using a TA. ...
... These include texture analyser (TA), 15 magnetic resonance imaging (MRI), 16 terahertz time-domain spectroscopy (THz-TDS) 17 etc. El-Arini and Clas 15 have studied the in vitro disintegration of fast-dissolving tablets using a TA. In this test, the tablet is attached to the tip of a flat-ended cylindrical probe by means of an adhesive tape which moves down in the liquid medium until a trigger force is detected. ...
Swelling‐based disintegration is considered important for drug release from tablets and can be modified with excipients called tablet disintegrants. Swelling of tablets occurs axially and radially, and most researchers have observed both these events separately using 2D images. In the current work, we have studied these events simultaneously instead of separately under a stereo microscope for tablet compacts composed of high proportions of disintegrants (sodium starch glycolate, SSG; and croscarmellose sodium, CCS), using water as the disintegrating medium. A hypothesis is proposed for the measurements of radial and axial swellings from a single 2D image, as horizontal lengths based on the Hipparchus trigonometric function for a right‐angle triangle. All predicted axial and radial lengths (as per proposed hypothesis) are found validated with respect to vernier caliper measurements for dry‐tablet compacts with a minute error of 3.809%. The axial swelling is ∼5‐folds more than that of radial swelling on the basis of normalized lengths. No particular trend can be spotted exclusively in favor of a superdisintegrant, however, the CCS‐based tablets have shown higher swelling as compared to SSG‐based tablets. From the current studies, it is evident that both axial and radial dimensions are obtainable from single 2D stereozoom images and can be successfully implemented for swelling studies of tablets. This article is protected by copyright. All rights reserved
... Over the last 20 years, efforts have been made to design in-vitro procedures resembling the in-vivo disintegration environment of FDTs, such approaches have been based on texture analysis (TA) (13), CCD cameras (charged-coupled device) (14), Kyoto models (KYO) (15), charged-coupled devices (16), Tricorptesters (17) and the Aston test (18). There are limitations associated with all of the recent in-vitro A flowchart describing the process of data collection and analysis of tablet disintegration measurements through digital imaging. ...
... Such flows of disintegration medium overestimate the volume that a tablet will be exposed to in the timeframe in which it disintegrates. Finally, many of the new assays model the process of disintegration with the incorporation of a mechanical perturbation to replicate forces associated with mastication, such as the TA test (5 kg over 60 s) and the Aston test (50 g for a fixed time) (13,16,18). The disintegration measurement while applying a force on the formulation does not replicate the disintegration forces encountered during clinical use. ...
Measuring tablet disintegration is essential for quality control purposes; however, no established method adequately accounts for the timeframe or small volumes of the medium associated with the dissipation process for fast disintegrating tablets (FDTs) in the mouth. We hypothesised that digital imaging to measure disintegration in a low volume of the medium might discriminate between different types of FTD formulation. A digital image disintegration analysis (DIDA) was designed to measure tablet disintegration in 0.05-0.7 mL of medium. A temperature-controlled black vessel was 3D-printed to match the dimensions of each tablet under investigation. An overhead camera recorded the mean grey value of the tablet as a measure of the percentage of the formulation which remained intact as a function of time. Imodium Instants, Nurofen Meltlets and a developmental freeze-dried pilocarpine formulation were investigated. The imaging approach proved effective in discriminating the disintegration of different tablets (p < 0.05). For example, 10 s after 0.7 mL of a saliva simulant was applied, 2.0 ± 0.3% of the new pilocarpine tablet remained, whereas at the same time point, 22 ± 9% of the Imodium Instants had not undergone disintegration (temperature within the vessel was 37 ± 0.5°C). Nurofen Meltlets were observed to swell and showed a percentage recovery of 120.7 ± 2.4% and 135.0 ± 6.1% when 0.05 mL and 0.7 mL volumes were used, respectively. Thus, the new digital image disintegration analysis, DIDA, reported here effectively evaluated fast disintegrating tablets and has the potential as a quality control method for such formulations.
... Several reviews on orodispersable tablets are available but none contained experimental data or were specified towards the lyophilised ODTs only (Rao et al., 2008;Ghosh et al., 2011;Rameesa and Drisya, 2015;Hirani et al., 2009;Velmurugan and Sundar, 2010). Furthermore, various ODT disintegration methods are available but these were not thoroughly tested on lyophilised tablets yet (El-Arini and Clas, 2002;Abdelbary et al., 2005). It is the aim of this research paper to map all the properties essential to a good functioning lyophilised ODT. ...
... At last, two texture analyzer methods were tested. The method described by El-Arini and Clas was compared to the one of Abdelbary et al. (test method 4), to evaluate if they were suited for a wide range of lyophilised ODTs (El-Arini and Clas, 2002;Abdelbary et al., 2005). These methods utilize a texture analyzer to mimic the forces applied to an ODT when present in the buccal cavity. ...
Orally disintegrating tablets (ODTs) produced by lyophilisation have a unique porous structure which leads to a favorable orodispersable functionality. They possess ultra-fast disintegration kinetics, have acceptable mechanical strength and give a smooth mouth texture. Only limited literature is available on the characterization of ODTs and even fewer on lyophilised tablets. The suitability of a broad range of characterization methods for lyophilised tablets was evaluated since they possess other mechanical properties compared to compressed tablets. Four ODTs with diverse properties were carefully selected and thoroughly analysed using various characterization techniques leading to a multitude of descriptors. The functionality of these four lyophilised tablets was examined and the relation between the different descriptors was evaluated using a Principal Component Analysis (PCA). Furthermore, μCT images of two ODTs were acquired to study the internal structure and active pharmaceutical ingredient (API) distribution inside the tablets. The important descriptors, disintegration and mechanical strength, interacted inversely indicating the importance of a well-balanced ODT formulation to achieve favorable properties. μCT data can improve the process knowledge as it yields very diverse descriptors. Ultimately, the different tablets were ranked at their performance.
... According to the European Pharmacopeia, orodispersible dosage forms include drug delivery systems that disintegrate in the patient's mouth in less than 3 min without the need of water. Specific methods using a texture analyzer to determine the disintegration time of these dosage forms have been described by Dor and Fix (2000) and El-Arini and Clas (2002). This approach presents the advantage of simulating the in vivo realistic conditions where the dosage form is in contact with very small volume of saliva (disintegration medium) and is subjected to some mechanical forces. ...
... The technique also allows the precise measurement of a very short disintegration time. In addition, this analytical method is valuable in discriminating between different formulations (El-Arini and Clas, 2002). In this study, the method was validated with regard to the volume of disintegration medium and the applied compression force. ...
Novel orally disintegrating system based on multiparticulate form was developed, offering an alternative to encounter major issues in the design of dosage form for pediatric patients, i.e. the difficulty in swallowing large solid dosage form (tablet or capsule), and the requirement to cover a broad range of doses for different age groups. Microcrystalline cellulose-based pellets containing acetaminophen were prepared via extrusion/spheronization followed by freeze-drying. The in vitro disintegration behavior of these pellets was quantitatively measured with a texture analyzer. Mercury intrusion and gas adsorption techniques, scanning electron microscopy of pellet surface and cross-section were performed in order to characterize their internal porous structure. Pellets characteristics such as size distribution, sphericity, friability and drug release were also determined. The developing process was able to produce pellets containing high drug loading (25, 50 and up to 75%, w/w) with good sphericity (aspect ratio ∼1) and low friability. The pellets exhibited an instantaneous disintegration upon contact with water, which was indicated by two parameters: the disintegration onset was approximating to 0, and the disintegration time less than 5seconds. The fast disintegration behavior is correlated with the pellet internal structure characterized by a capillary network with pore diameter varying from 0.1 to 10μm. Such a structure not only ensured a rapid disintegration but it also offers to freeze-dried pellets adequate mechanical properties in comparison with conventional freeze-dried forms. Due to pellet disintegration, fast dissolution of acetaminophen was achieved, i.e. more than 90% of drug released within 15minutes. This novel multiparticulate system offers novel age-appropriate dosage form for pediatric population owing to their facility of administration (fast disintegration) and dosing flexibility (divided and reduced-size solid form).
... In order to solve this problem development of solid dosage that disintegrate rapidly or dissolve even when taken orally without water is being undertaken [3,4,5,6]. These novel type of tablets that disintegrate/ dissolve/ disperse in saliva in less then a minute without the need of water [7]. Their characteristic advantage such as administration without water, any where, any time lead to their suitability to geriatric and pediatric patients. ...
The aim of present study is to exist a novel super disintegrants in fast dissolving tablet. Guar gum is a natural substance and used in many pharmaceutical product and it can also used as a super disintegrating agent in fast dissolving tablet. The result is that it released the 99.21% drug in 15min as compared to Sodium Starch Glycolate (SSG), where only 97.51% drug was released. The onset of time was better for guar gum where, 84.79% of drug was released in 2min from F3 formulation as compared of F6 formulation where only 71.22% drug was released. The possible mechanism of disintegrating property was good swelling property of guar gum than SSG but when the concentration of guar gum was used above 8%, it created a problem on disintegration of tablet due to formation of gel layer around the tablet. All evaluating parameters were within range and no markedly difference was observed.
... The usage of texture analysers can be applied to various dosage forms. They have been used to optimise the adhesiveness and cohesiveness of water-in-oil emulsions [46], disintegration behaviour of fast-dissolving preparations [47] and evaluation of the mucoadhesive properties of various polymers [48]. In addition, texture analysers can be employed to investigate the swelling and erosion behaviour of matrix tablets in correlation with their drug liberation [49]. ...
Gel layer characteristics play a crucial role in hydrophilic hydroxypropyl methylcellulose (HPMC) matrix development. Effervescent agents have the potential to affect the gel layer microstructures. This study aimed to investigate the influence of effervescence on the microstructure of the gel layer around HPMC matrices using a combination of texture analysis and imaging techniques. The relationship with drug release profile and release mechanisms were also examined. The high amounts of effervescent agents promoted a rapid carbonation reaction, resulting in a high gel layer formation with a low gel strength through texture analysis. This finding was ascribed to the enhanced surface roughness and porosity observed under digital microscopy and microporous structure of the gel layer under scanning electron microscopy. The reconstructed three-dimensional images from synchrotron radiation X-ray tomographic microscopy notably exhibited the interconnected pores of various sizes from the carbonation reaction of effervescent and microporous networks, indicating the gel layer on the tablet surface. Notably, effervescence promoted the increase in interconnected porosities, which directly influenced the strength of the gel layer microstructure, drug release patterns and release mechanism of the effervescent matrix tablet. Therefore, combined mechanical characterisation and imaging techniques can provide new insights into the role of effervescent agents on the gel layer microstructure, and describe the relationship of drug release patterns and release mechanism of matrix tablets.
... A slightly flattened silicone pipe with 4 mm holes is used as a disintegration bed. A flow of water (10 ml/min) through the holes simulated saliva and the interaction of media with the tablet lead to disintegration, which subsequently is measured by a texture analyzer [67]. Each test was repeated eight times, and disintegration time was calculated by the plot of distance/time [61]. ...
Orally disintegrating tablets (ODTs) rapidly disintegrate or dissolve in the oral cavity without using water. Demand for ODTs has increased, and the field has overgrown in the pharmaceutical industry and academia. It is reported that ODTs have several advantages over other conventional tablets. Since some of them are absorbed from the mouth, pharynx, and esophagus as the saliva passes down into the stomach, in such cases, the bioavailability of the drug improves meaningfully. Furthermore, the immediate release property of ODTs makes them a popular oral dosage form in patients with swallowing challenges, children, and for cases with a need for rapid onset of action. The current review article explains the features of active ingredients and excipients used in the formulation of ODTs, discusses multiple ODT formulation and preparation techniques with their merits and demerits, and also, offers remedies for problems associated with ODTs. Moreover, quality control steps and required considerations are presented.
... The test velocity was set at 0.5 mm/s with a compression depth of 5 mm and the trigger load of 100 g. In a typical process, the tablets were placed vertically inside the device and the probe landed on it with the mentioned velocity and compression depth [18]. The samples were evaluated 1 h and 30 days after production for shelf life by monitoring the hardness. ...
Nowadays, consumers pay attention to the health-related properties of the food as well as their nutritional worth. Rice bran includes high amounts of proteins, fats, minerals, B vitamins and dietary fibers. These properties can contribute to health enhancement through declining the rate of cancer, cardiovascular diseases, renal stones and hyperlipidemia. In this study, the influence of gelatin, xanthan, and guar gums (at 0, 5, and 10%) on the physicochemical, shelf life, sensory and image properties of functional rice bran tablets was investigated. The results displayed that the gums addition leads to changes of tablets chemical properties. The acidity and peroxide content of the gum-containing samples was significantly lower than the control sample. The highest amount of disintegration time, hardness and moisture content was observed in samples containing 10% xanthan in first and 30th days of storage. Sensory analysis revealed that gelatin, xanthan and guar did not significantly affect the color, aroma, taste and flavor of the rice bran tablets. Sensory panelists liked the samples containing 10% xanthan in terms of texture and overall acceptance as an excellent food supplement. Principal component analysis (PCA) allowed categorizing specialties. Partial least squares regression (PLSR) models were applied to find out the relationships between sensory and instrumental data.
... Dissolution rate and bioavailability of poorly-water soluble drug formulations can be improved by the homogeneous and consistent mixing of ingredients, in a twin screw extruder. This provides better mixing to produce a homogeneous solid containing finely dispersed drug [42][43][44][45][46][47] ...
Introduction: Sublingual drug delivery can be an alternative and better route when compared to oral drug delivery as sublingually administered dosage forms bypass hepatic metabolism. A rapid onset of pharmacological effect is often desired for some drugs, especially those used in the treatment of acute disorders. Sublingual tablets disintegrate rapidly and the small amount of saliva present is usually sufficient for achieving disintegration of the dosage form coupled with better dissolution and increased bioavailability. Approach: Published articles from PubMed and other standard sources were utilized to review and compile an overview of sublingual tablets and the benefits of the sublingual route of administration. Findings: Sublingual tablets were found to have better characteristics when compared to conventional dosage forms. Sublingually administered tablets achieved better bioavailability, rapid onset of action and better dissolution properties due to fast disintegration. The addition of super-disintegrants facilitated rapid disintegration and this approach can be used to treat acute disorders or emergency conditions. Conclusion: Sublingual tablets or any sublingual dosage form can be used to achieve a rapid onset of action, better patient compliance and increased bioavailability. The sublingual route of administration can be used for drugs which undergo extensive first pass metabolism or degradation in the GIT. Drugs administered sublingually tend to have better bioavailability which correlates to dose reduction when compared to conventional oral tablets.
... Theories of Dissolution: [9] 1) Diffusion Layer Model (Film Theory) 2) Danckwert's Model (Penetration or Surface Renewal Theory) 3) Interfacial Barrier Model (Double Barrier Mechanism OR Limited Solvation Theory) ...
... Not only acceptable in terms of BP, formula 33 had faster mouth disintegration than orodispersible tablets prepared by other researchers (15) and also faster than some of the commercialized products. For example, the disintegration time in the mouth of Benadryl® (USA), DuraSolv® (USA), Nimesulide® (Switzerland) and Nippon® (Japan) orodispersible tablets are 40, 45, 30 and 30 sec, respectively (16,17) as shown in figure (2). ...
Abstract
Metoclopramide HCl (MTB) is a potent antiemetic drug used for the treatment of nausea and vomiting. Many trials were made to prepare a satisfactory MTB orodispersible tablet using direct compression method.Various super disintegrants were used in this study which are croscarmellose sodium (CCS), sodium starch glycolate (SSG) and crospovidone (CP). The latter was the best in terms of showing the fastest disintegration time in the mouth.Among the different diluents utilized, it was found that a combination of microcrystalline cellulose PH101 (MCC 101), mannitol, dicalcium phosphate dihydrate (DPD) and Glycine was the best in preparing MTB orodispersible tablet with
fastest disintegration time in the mouth.The physical parameters of the prepared MTB orodispersible tablet were satisfactory as hardness (4 Kg), friability (0.5%) and mouth disintegration (23 sec).The overall results suggest that the prepared formula of MTB as orodispersible tablet could be utilized as a new dosage form for the oral administration.
... For some ODTs, disintegration may even be used in quality control as an alternate to a formal dissolution test. Alternative tests have been proposed that do not utilize the compendial apparatus (2,3). ...
The USP <701> basket-rack assembly with disks is applied to the disintegration testing of orally disintegrating tablets (ODTs). Although <701> is generally suitable for testing ODTs as described, interference arising from the physical interaction of the tablet and disk is observed for many ODTs. Described herein is an innovative yet simple modification to the commercially available disk, developed to circumvent this interference and allow for testing a wider range of tablets. The ‘footed disk’ modification is practical in that it uses materials that are readily available, maintains correct density, and produces no interference during execution of the test procedure. These characteristics support a favorable status for the application of a modified disk for testing ODTs in individual regulatory filings.
... The TA probe provides a constant force that considers the forces produced by the tongue on the ODDT. Substituting distilled water with simulated saliva can produce a more accurate repre- sentation of the oral cavity (Figure 4) 96,100 . A limitation of this method is that the adhesive material utilized to affix the ODDT to the probe, obstructs the exposure of the drug surface to the Figure 4. Schematic representation of (a) a TA used for in vitro disintegration testing of ODDTs; (b) the detailed operating structure of the disintegration recipient; (c) the assembled operating structure of the disintegration recipient and (d) digital image demonstrating hardness testing of ODDTs (Adapted from: Abdelbary et al. 101 ). ...
Purpose:
A 3D-Bioplotter® was employed to 3D print (3DP) a humic acid-polyquaternium 10 (HA-PQ10) controlled release fixed dose combination (FDC) tablet comprising of the anti-HIV-1 drugs, efavirenz (EFV), tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC).
Methods:
Chemical interactions, surface morphology and mechanical strength of the FDC were ascertained. In vitro drug release studies were conducted in biorelevant media followed by in vivo study in the large white pigs, in comparison with a market formulation, Atripla®. In vitro-in vivo correlation of results was undertaken.
Results:
EFV, TDF and FTC were successfully entrapped in the 24-layered rectangular prism-shaped 3DP FDC with a loading of ∼12.5mg/6.3mg/4mg of EFV/TDF/FTC respectively per printed layer. Hydrogen bonding between the EFV/TDF/FTC and HA-PQ10 was detected which was indicative of possible drug solubility enhancement. The overall surface of the tablet exhibited a fibrilla structure and the 90° inner pattern was determined to be optimal for 3DP of the FDC. In vitro and in vivo drug release profiles from the 3DP FDC demonstrated that intestinal-targeted and controlled drug release was achieved.
Conclusion:
A 3DP FDC was successfully manufactured with the aid of a 3D-Bioplotter in a single step process. The versatile HA-PQ10 entrapped all drugs and achieved an enhanced relative bioavailability of EFV, TDF, and FTC compared to the market formulation for potentially enhanced HIV treatment.
... Thus, a more effective and discriminating method for determining disintegration characteristics of ODTs was needed. Several methods for testing disintegration time of ODTs were reported using a texture analyzer, [28][29][30][31][32][33]40 and we modified these methods by employing conditions more closely related to in vivo conditions. These include: (1) using 2.0 mL of freshly prepared simulated salivary fluid instead of water; (2) using convex tablet instead of cylindrical tablet to minimize the contact area between the tablet and the container, which allows more ready interaction between fluid and tablet; and (3) using a smaller contact force (3.0 N) between probe and tablet to avoid breaking the tablet by applied force instead of disintegration of tablet by water penetration. ...
To develop a palatable direct compression (DC) orally disintegrating tablet (ODT) product of a bitter drug, diphenhydramine (DPH), using an integrated crystal and particle engineering formulation development approach. A DPH salt with a sweetener, acesulfame (Acs), DPH-Acs, was synthesized and its solid state properties were comprehensively characterized. Tablet formulation composition and compaction parameters were optimized by employing material sparing techniques. In vivo disintegration time, bitterness, and grittiness of the final ODT product, were evaluated by a taste panel. Physical stability of the ODT tablets was assessed to identify appropriate storage conditions. Phase-pure DPH-Acs exhibited significantly better tabletability and palatability than DPH-HCl. A DC formulation was designed and optimized to obtain a new ODT product with good manufacturability and excellent product characteristics, including faster in vivo disintegration, and acceptable bitterness and grittiness. The entire development activities required only 15 g of DPH and a period of two months. A new ODT product of DPH with excellent pharmaceutical properties was successfully developed in a short time. This example shows that integrated crystal and particle engineering is an effective approach for developing high quality ODT products using the DC process.
... Rapid disintegration studies were undertaken on the U-D-WAF formulations using the method as outlined by El-Arini et al. [17] with modifications. A Texture Analyzer (TA.XTplus Stable Microsystems, Surrey, UK) equipped with a flat, cylindrical probe (20 mm diameter), was used to mimic the tongue's influence on the U-D-WAF. ...
The purpose of this study was to design and evaluate the performance of an Ultra-fast Disintegrating Wafer (U-D-WAF) loaded with highly water soluble diphenhydramine hydrochloride (DPH) through the oramucosa of the Large White Pig model. For the first time this work explored the oramucosivity of the U-D-WAF by detailed molecular modeling of the matrix on buccal tissue in order to mechanistically deduce the mucodhesivity. The U-D-WAF was formulated using a blend of hydroxypropylcellulose, poly(acrylic) acid, sodium starch glycolate and β –cyclodextrin in accordance with a Box-Benkhen experimental design for optimization prior to ex vivo permeation and in vivo release studies in the Large White Pig. Molecular simulation studies assess the mucoadhesivity of the U-D-WAF to the oramucosa. A mean Drug Entrapment Efficiency of 72.96 ± 4.32%, disintegration time of 29.33 ± 15.91 s and drug release after 60 s of 86.32 ± 20.37% was recorded. Ex vivo permeation studies revealed cumulative drug permeation of 86.32 ± 20.34% 60 s after onset. In vivo evaluation of the optimized U-D-WAF had a Cmax = 59 μgL⁻¹ approximately 300 s after administration. The ultrafast disintegration of the U-D-WAF matrix with desirable mucoadhesivity in in vitro and in vivo studies makes it suitable for effective and rapid oramucosal drug delivery.
... With the ability to detect morphological changes during disintegration, the authors suggest that their method would have utility both in formulation development and quality control. El-Arini et al. (32) described the use of a texture analyzer (TA) in which the flat-ended cylindrical probe penetrates into the disintegrating tablet while it is immersed in water. The results are plots of distance moved by the probe under a small set force as a function of time. ...
Orally disintegrating tablets (ODTs) are solid single-unit dosage forms that are designed to be placed in the mouth, allowed to disperse or dissolve in the saliva, and then swallowed without the aid of additional water. Despite a surge of orally disintegrating tablets in the market in the recent years, they potentially can be confused with other solid oral dosage forms that are consumed without additional water intake, including lozenges, buccal tablets, and chewable tablets. Lozenges and buccal tablets are intended to dissolve slowly in the mouth, whereas, orally disintegrating tablets must disperse or dissolve in the mouth quickly, within seconds. Chewable tablets are also different from orally disintegrating tablets because they require manual chewing action by the patients before they can be swallowed. The disintegration times are longer for the chewable tablets compared to the orally disintegrating tablets. For a tablet to be classified as an orally disintegrating tablet the disintegration time should be sufficiently rapid for the patient to not feel the need or compulsion to chew. Orodispersible tablets (1), rapidly disintegrating tablets (2), and fast-dissolving tablets (3) have been used as synonyms for orally disintegrating tablets. Examples of orally disintegrating tablets include over-the-counter drugs such as Claritin® RediTabs® (loratadine rapidly-disintegrating tablets) and Alavert™ (loratadine orally disintegrating tablets), and prescription drugs such as Maxalt-MLT™ (rizatriptan benzoate) and ZOFRAN® (ondansetron) Orally Disintegrating Tablets.
... The TA probe provides a constant force that considers the forces produced by the tongue on the ODDT. Substituting distilled water with simulated saliva can produce a more accurate representation of the oral cavity (Figure 4) 96,100 . A limitation of this method is that the adhesive material utilized to affix the ODDT to the probe, obstructs the exposure of the drug surface to the dissolution medium; unlike in the oral cavity, where all surfaces of the system will have some interaction with the saliva 94,100 . ...
The drug treatment of acute disorders such as neuropathic pain, migraines, insomnia, vomiting, allergic rhinitis or erectile dysfunction requires an immediate pharmacological effect that may be achieved through parenteral drug administration. However, the parenteral route is not always convenient for reasons that are well known. Therefore, in the recent past there has been a barrage of interest in formulating new, non-invasive, reliable and convenient oradispersible drug delivery technologies (ODDTs). Research in this area has focused extensively on developing ODDTs that are capable of releasing drugs immediately when they come into contact with saliva. This disregards the necessity of water during administration and several other advantages that is an attribute that makes this technology lucrative for groups such as pediatrics, geriatrics, psychiatrics and unconscious patients. Many reviews have been compiled on the salient features of ODDTs. However, none to date has focused on the actual formulation techniques used to produce these technologies and how this may impact their disintegration and physical stability for fulfilling their purpose. Therefore this review provides a concise incursion on the recent formulation techniques, excipients used as well as methods of testing the performance of ODDTs and critically assesses these in terms of improving their performance.
... The time for the tablet to disintegrate is determined by measuring the distance the probe traveled into the tablet. Typical time-distance profiles generated by the Texture Analyzer software enabled the calculation of beginning and ending of disintegration time [40]. ...
The solid dosage form that dissolves or disintegrates quickly in the oral cavity, resulting in solution or suspension without the need of administration of water is known as oral fast dispersing/dissolving dosage form or mouth-dissolving tablets. Mouth dissolving tablets dissolve rapidly in the saliva without the need for water, releasing the drug. Some drugs are absorbed from the oral cavity as the saliva passes down into the stomach. In such cases, bioavailability of drug is significantly greater than those observed from conventional tablet dosage form. This article describes the existing techniques for fast dissolving oral preparation, highlights their manufacturing processes, evaluation parameters and future trends for these evolving dosage forms.
... Using a charge couple device camera or texture analyser disintegration time was noted at the time when tablet was completely disintegrated and passes through the screen of sinker [114][115] . New modified in-vitro methods had been developed by diverse scientists for precisely determining disintegration time using a texture analyser instrument [116] . This method employs a flat ended cylindrical probe that penetrates into the disintegrating tablet which was kept immersed in water. ...
Nowadays orally disintegrating drug delivery systems (ODDDSs) were exploited extensively not only to improve the performance of delivery system and the patient compliance but also for managing the life cycle of the product and generating opportunities. Present review work was aimed to explore technical aspects and issues related to ODDDSs development and evaluation techniques so as to aid designing an efficient orally disintegrating delivery system. In this respect data were collected from databases, compiled and analysed. Presented data will help pharmaceutical scientists engaged in designing ODDDSs for enhancing its potentiality to improve performance and patient compliance.
... The probe moves until a trigger force is detected at which point the TA is set to maintain a predetermined nominal force for a given period of time (60 s). As the tablet starts disintegrating, the TA measures the penetration distance as the tablet is compressed while submerged in the medium [12]. ...
The concept of Fast Dissolving Drug Delivery System emerged from the desire to provide patient with conventional mean of taking their medication. Difficulty in swallowing (Dysphagia) is a common problem of all age groups, especially elderly and pediatrics, because of physiological changes associated with these groups of patients. Solid dosage forms that can be disintegrated, dissolved, or suspended by saliva in the mouth resulting in easy swallowing can provide significant benefits to the pediatric and geriatric population, as well as other patients who prefer the convenience of easily swallowable dosage forms. the dosage forms developed to facilitate ease of medication, the Fast-disintegrating/dissolving tablets (FDT's) is one of the most widely employed as commercial products. The FDT has remarkable disintegration properties; without water, it is rapidly disintegrated in the mouth within only a few seconds. When the FDT is placed in the oral cavity, saliva quickly penetrates into the tablet causing rapid disintegration. One of the most important characteristics of the FDT is its disintegration time in the oral cavity; however, a suitable method to access the disintegration properties described in the official books has not been developed. It is difficult to assess the disintegration rate for the FDT with these tests due to its rapid disintegration rate even in a small amount of water. To overcome this problem, several new methods have been proposed. The purpose of this review is to establish a suitable disintegration method for FDT.
... 6) A texture analyzer is employed, and a flatended cylindrical probe penetrates the disintegrating tablet immersed in water. Many scientists [7][8][9][10] have developed new automatic in vitro methods to quantitatively evaluate the disintegration time of ODTs, however, all attempted to measure the end-point of the process were not dynamic tablet disintegration process. ...
To measure the rapid disintegration of Oral Disintegrating Tablets (ODT), a new test (XCT) was developed using X-ray computing tomography (X-ray CT). Placebo ODT, rapid disintegration candy (RDC) and Gaster®-D-Tablets (GAS) were used as model samples. All these ODTs were used to measure oral disintegration time (DT) in distilled water at 37±2ºC by XCT. DTs were affected by the width of mesh screens, and degree to which the tablet holder vibrated from air bubbles. An in-vivo tablet disintegration test was performed for RDC using 11 volunteers. DT by the in-vivo method was significantly longer than that using the conventional tester. The experimental conditions for XCT such as the width of the mesh screen and degree of vibration were adjusted to be consistent with human DT values. Since DTs by the XCT method were almost the same as the human data, this method was able to quantitatively evaluate the rapid disintegration of ODT under the same conditions as inside the oral cavity. The DTs of four commercially available ODTs were comparatively evaluated by the XCT method, conventional tablet disintegration test and in-vivo method.
... Authors attempted to gain correlation between the in vivo tablet disintegration time and the tableting parameters (Shibata et al., 2004), disintegration time of tablets in agitated fluid (Sunada and Bi, 2002), disintegration of tablets due to mechanical force (Harada et al., 2006), disintegration of tablets followed by CCD camera (Morita et al., 2002), etc. One of the most promising instrumental methods to predict the disintegration times of fast disintegrating tablets is the use of texture analyzers (texture analysis method), where the instrument can follow the structural changes (softening) of tablets during the disintegration process (Dor and Fix, 2000;El-Arini and Clas, 2002). Abdelbary et al. (2005) investigated five different ODT formulations using texture analyzer with constant load (50 g). ...
One of the promising approaches to predict in vivo disintegration time of orally disintegrating tablets (ODT) is the use of texture analyzer instrument. Once the method is able to provide good in vitro in vivo correlation (IVIVC) in the case of different tablets, it might be able to predict the oral disintegration time of similar products. However, there are many tablet parameters that influence the in vivo and the in vitro disintegration time of ODT products. Therefore, the measured in vitro and in vivo disintegration times can occasionally differ, even if they coincide in most cases of the investigated products and the in vivo disintegration times may also change if the aimed patient group is suffering from a special illness. If the method is no longer able to provide good IVIVC, then the modification of a single instrumental parameter may not be successful and the in vitro method must be re-set in a complex manner in order to provide satisfactory results. In the present experiment, an optimization process was developed based on texture analysis measurements using five different tablets in order to predict their in vivo disintegration times, and the optimized texture analysis method was evaluated using independent tablets.
... This rapid disintegration of tablets was due to the presence of the pores resulting in faster penetration of medium leading to swelling and wicking of superdisintegrants, creating hydrodynamic pressure inside the tablets for quick and complete disintegration of the tablet. [32,33] The tablet (T4) containing superdisintegrants in the ratio of 1 : 0.5 (SSG and Pharmaburst) disintegrated faster than tablets prepared with other ratios (1 : 0.25, 1 : 0.75, and 1 : 1). The in vitro drug release from tablet containing solid dispersion of PIO (T4) was 93.52 ± 3.05% and drug release of tablet containing pure PIO (T1) showed drug release of 42.12 ± 2.14%, whereas MFs released 45.23 ± 1.0% of drug within 60 minutes [ Table 4]. ...
Investigation of in vitro/in vivo behavior of fast-dissolving tablets containing solid dispersions of pioglitazone hydrochloride (PIO) is the focus of the present research work. The effect of various hydrophilic polymers on the aqueous solubility of PIO was studied. Poly vinyl pyrrolidine K 30 (PVPK 30) carrier was selected and solid dispersions were prepared by various methods. Evaluation of solid dispersion for percentage yield, drug content, solubility, and Fourier Transform Infrared-indicated kneading method was most appropriate. Furthermore, the dissolution studies exhibited an enhancement in drug dissolution. One-way ANOVA of in vitro data suggested that there was significant (P ≤ 0.05) difference in dissolution profile of PIO solid dispersion when compared with pure drug and commercial product. Infrared spectroscopy, differential scanning calorimetry, and powder X-ray diffraction performed on solid dispersion indicated lack of physicochemical interaction between the drug and the carrier. The selected formulation is compressed into fast-dissolving tablets which were further evaluated for tablet properties and in vitro drug release. In vivo studies of pure drug, selected formulation, and marketed product were carried out in male Wistar rats and pharmacokinetic parameters were calculated using Kinetica software 2000. The best formulation has shown T(max) of 1 hour which was highly significant (P < 0.01) when compared with pure drug and marketed formulation. Therefore, the solid dispersions prepared by kneading method using PVPK 30 as hydrophilic carrier can be successfully used for improvement of dissolution of PIO and resulted in faster onset of action as indicated by in vivo studies.
A sublingual tablet is a medication formulation that dissolves beneath the tongue, facilitating quick absorption of the active ingredients through the mucous membranes and into the bloodstream. Bypassing the liver metabolism and digestive tract, this technique can improve the effectiveness and speed of medication delivery. Sublingual medications are frequently used for drugs that need to start working quickly. Benefits of the sublingual route include a more consistent therapeutic impact and the avoidance of stomach upset. The salient features of the sublingual tablet include its ability to dissolve beneath the tongue, its speedy absorption and beginning of action, and its ability to prevent gastrointestinal irritation.
Orodispersible tablets (ODTs) represent a growing category of dosage forms intended to increase the treatment acceptability for special groups of patients. ODTs are designed to rapidly disintegrate in the oral cavity and to be administered without water. In addition, ODTs are easy to manufacture using standard excipients and pharmaceutical equipment.
This study adds to previously published research that developed an instrumental tool to predict oral disintegration and texture-related palatability of ODTs with different formulations. The current study aimed to challenge the predictive capacity of the models under variable process conditions. The studied process parameters with potential impact on the pharmaceutical properties, texture profiles, and palatability were the compression pressure, punch shape and diameter. Subsequently, for all the placebo and drug-loaded ODTs, the in vivo disintegration time and texture-related palatability were determined with healthy volunteers.
Mouth dissolving tablets are well established dosage forms available in the market. The numerous advantages that they offer to the patients in terms of compliance as well as to the manufacturers in terms of huge revenues by line extension of products are well known. In spite of such popularity, there seems to be lack of a standardized system to characterize these dosage forms. Enormous work has been done in this field, wherein some of the researchers have developed their own methods of evaluation. This article attempts to present a detailed review regarding technological advances made so far in the area of evaluation of mouth dissolving tablets with respect to special characteristics of these unique dosage forms. In the absence of any available standardized method, the author’s recommendation on critical issues in the field may be considered.
Orally disintegrating tablets (ODTs) are the preferred and accepted solid dosage forms by patients. These tablets disintegrate in the oral cavity within a short period, providing an advantage for individuals who have difficulty swallowing. Quality control of ODTs can be achieved through measures such as friability, porosity, hardness, wetting time, water absorption capacity, in vitro disintegration test, and dissolution test. This article summarizes the advantages and in vitro quality control tests of orally disintegrating tablets.
Direct compression method can be considered as an important method for the formulation of fast dissolving tablets of Domperidone compare to wet granulation method. The rank order for the best 3 formulations is F2>F1. Formulation F2 having DCP as the super disintegrant is the best formulation of all. Higher the concentration of the lubricating agent (Magnesium Stearate or Talc), higher will be the disintegration time. Formulation having the better Super disintegrants (Ac-Di-Sol) will have better in vitro disintegration time and dissolution along with lesser friability and weight variation. Thus, it may be concluded that the fast-dissolving tablets of Domperidone can be successfully prepared and undoubtedly the availability of various technologies and manifold advantages of fast dissolving tablets will surely enhance patient compliance and its popularity in the near future.
In current studies, the disintegration process of tablets has been studied by thermal imaging. The study covers two major aspects; first, new revelations in the mechanism of tablet disintegration, and second, the development of disintegration test as a multi-point test by new thermometric and non-thermometric methods. The study has been carried out on fexofenadine rapidly disintegrating tablets (FEX RDTs) in a dark room cabinet fitted with a Fluke thermal imager and using water as the disintegration medium. The studies exhibit the existence of endothermic peaks during the early penetration of water in FEX RDTs. These endotherms are prominent at the starting point when the disintegration has just started, or the tablet has been just exposed to the water. Such endotherms have not been reported earlier for tablets and can be considered as a part of the wicking mechanism during disintegration. In later stages, when the water has completely wet the tablet, the endotherms are superimposed by exotherms. The endotherms or exotherms have also been used as a measurement of disintegration in the form of a new thermometric parameter, “area under temperature curve” (AUTC). Non-thermometric disintegration profiling by residual and subtraction methods is also performed. Among these, disintegration by the residual method, i.e., disintegration (residual) is newly introduced. In the end, the principal component analysis (PCA) describes the relationship between various disintegration methods, particle size distribution, and dissolution. PCA reveals that AUTC is the best method for studying the disintegration behavior of FEX RDTs.
Oral Disintegrating Tablets of Triazolam were formulated with an aim to improve the versatility, patient compliance, and accurate dosing. The formulations ere developed with an objective to use by the pediatric and geriatric patients. Triazolam Oral Disintegrating Tablets were prepared by direct compression method using cross povidone, croscarmellose sodium, sodium starch glycolate and combinations of CP+CCS, and CP + SSG as super disintegrates exhibited good pre-formulation and tableting properties of three super disintegrates, the formulation contained combination of CP + CCS showed better performance in terms of disintegration time when compared to other formulations. Order of the super disintegrates activity is as follows. (CP + CCS) > (CP + SSG) > CP > CCS >SSG The formulation F15 was found to be the best among all twenty Triazolam ODT formulations because it has exhibited faster disintegration time (17.66 sec) when compared to the other formulations and it showed 99.87±0.18% drug release at the end of 25 min. Triazolam Oral Disintegrating Films were prepared by solvent casting method using different grades of Hydroxypropyl Methyl Cellulose like HPMC – E15, HPMC – 5cps, HPMC – 50cps. Based on disintegration and dissolution results it was concluded that the formulation F15 contained CP 5% + CCS 5% was the best formulation among all otherformulations.
The main objective of this work is to formulate and evaluate Cetirizine HCl MFDT’s using different concentrations of superdisintegrants like croscarmellose sodium (CCS), sodium starch glycolate (SSG) and their combinations in different ratios. The in vitro disintegration time of Cetrizine Hcl prepared by direct compression method by super disintegrates were found to be in the range of 18 to 11sec fulfilling the official requirements. The bulk density and tapped bulk density for the entire formulation blend varied from 0.508 gm/cc to 0.5438 gm/cc and 0.5941 to 0.6408 respectively. The friability was found in all designed formulations in the range 0.42 to 0.74% to be well within the approved range (<1%). The weight variation was found in all designed formulation in the range 97 to 102 mg. The wetting time were found to be in the range of 11 to 18sec. Water absorption ratio for all the formulations found in the range 11 to 16%.combination of sodium starch glycolate and cross carmellose sodium (6% of 25%-ssg&75%ccs)) promotes dissolution rate of drug release when compared to formulation of SSG & CCS alone. It may be due to capillary and wicking mechanism of SSG & CCS. Keywords:
An orally disintegrating tablet is a novel formulation that dissolves in the saliva within a few seconds and without requiring of drinking additional water. This dosage form is a powerful way to deliver active drugs ingredients because it has many advantages. Many studies have compared this form of tablet with the ordinary forms in vitro and in vivo and found that orally disintegrating tablets have superior patient compliance and drug solubility. However, there are some criteria for the active pharmaceutical ingredients to prepare tablets as fast dissolve forms. There are several ways to prepare this dosage form and each method has its pros and cons. Technologies of preparation and various examples of orally disintegrating tablet available in the market using different preparing procedures are presented in this review. Taste masking is required form some active pharmaceutical ingredients to be formed as orally disintegrating tablets. In vitro evaluation and quality control measures of orally disintegrating tablet is also discussed in this review.
Orally disintegrating tablets (ODTs) are attractive oral solid dosage forms as it has significant impact on the patient compliance. ODTs disintegrate and/or dissolve rapidly in the saliva without the need for water and offer an advantage for populations who have difficulty in swallowing. There seems to be lack of a standardized system to characterize ODTs. Evaluation of ODTs can be done by friability, hardness, wetting time, water absorption ratio, in vitro disintegration test and dissolution test. The current article summarizes in vitro quality control tests and clinical studies for ODTs.
Orally disintegrating tablets (ODTs) are most preferred and accepted solid dosage forms by the patients. These tablets disintegrate in the saliva in the mouth within a short period of time and offer an advantage for populations who have difficulty in swallowing. Quality control of orally disintegrating tablets can be done by friability, porosity, hardness, wetting time, water absorption capacity, in vitro disintegration test and dissolution test. This article summarizes advantages and in vitro quality control tests of orally disintegrated tablets.
Fast Dissolving Tablets have emerged as one of the most popular and widely accepted dosage forms, especially for the pediatric and geriatric patients. To obviate the problem of dysphasia and to improve patient compliance, FDTs have gained considerable attention as preferred alternatives to conventional tablet and capsule formulations. Various scientific techniques including freeze drying, moulding, freeze drying, sublimation, direct compression, cotton candy process, mass extrusion, melt granulation etc. have been employed for the development of FDTs. These techniques render the disintegration of tablet rapidly and dissolve in mouth without chewing or additional water intake. The current article is focused on ideal characteristics, advantages, methods of preparation, superdisintegrants, and evaluation parameters.
The objective of this study was to find out the effect of starch paste and guar gum grade 4000 on hardness and disintegration of fast dissolving tablet by using one way ANOVA, polynomial equation and graphical presentation. As model formulations 9 formulations were prepared by using 32 factorial designs. The formulation variables, starch paste concentration and guar gum concentration were selected as the independent variables while hardness and disintegration time were selected as the dependent variables. A substantial better hardness (6.0±0.28) and low disintegration time of tablet (18±0.40) were at +1level of X1and X2.By one way ANOVA the F-value (11.98 and 3.88) and P- value (0.0438 and 0.0007) demonstrated that starch paste and guar gum were given significant effect on hardness and disintegration time of tablet. The polynomial equation was demonstrating the combined effect of both independent variables on dependent variable. The hardness was mainly effected by starch paste (b2=-0.78) but minutely effected by guar gum (b1=-0.58), that was also demonstrated by graphical presentation. The disintegration time was mainly affected by guar gum concentration (b1=-100) but minutely affected by starch paste (b2=-0.33), that was also demonstrated by graphical presentation.
Mouth Melt Tablets (MMT) are being marketed only since a few years. The European Pharmacopoeia describes mouth melt tablets for the first time in 2002. Due to easy application the popularity of MMT increases especially in the field of children's or geriatric medicine. This is a growing market, what is correlating with an increasing number of patent applications. For research and development in the field of pharmaceutical technology it is often necessary to determine and describe the process of the disintegration of mouth melt tablets. Thus the influence of different manufacturing parameters can become apparent. The effects of different ingredients on the dissolution rate can be analysed as well. Moreover, determining the disintegration rate of mouth melt tablets is a very important criterion of quality control. The dissolution method described in the European Pharmacopoiea does not allow to completely characterize this process. It was the aim of joint project to examine and describe exactly and realistically very small differences in the dissolution parameters of a selection of commercially available mouth melt tablets. The obtained results should allow to improve the pharmaceutical-technological formulation and procedure development for mouth melt tablets. Several methods for the determination of the disintegration time were compared. The method used in the following publication leads to highly reproducible results. Hereby the dissolution rate, starting and ending point of the dissolution procedure, the dissolution profile, the penetration way of the punch, the difference between band height and penetration way are important parameters.
A novel ultrasound-assisted enzymatic technology was developed to approximately process cellulose cortex of brown rice. The total sugar content change, the viscosity properties of brown rice flour, the water absorption and cooking properties of brown rice after enzyme treatment were tested. With the increasing time for cellulase, pecti-nase and their complex to hydrolyze cellulose cortex of brown rice under ultrasound, the total sugar content was continuously increasing, and after 2.5 h of treatment, it reached 61.41 mg, 77.58 mg and 95.31 mg respectively, which was 1.16, 1.06 and 1.47 times higher than that in the enzyme treatment without ultrasound assistance, respectively. It was demonstrated that the low-frequency ultrasound have certain stimulative effect for the three enzymes on hydrolyzing cellulose cortex of brown rice, especially for the complex enzyme. The peak viscosity, trough viscosity and final viscosity were all increased, and with the decomposition of cellulose cortex of brown rice, the water absorption capability of treated brown rice was enhanced, as well as the moisture content after being balanced. The hardness, adhesiveness, chewiness and resilience of cooked brown rice have a significantly negative correlation(P<0.05) with the total sugar content hydrolyzed and the correlation coefficients were -0.828, -0.837, -0.853, -0.827, respectively. In a word, ultrasound assisted enzymatic treatment can be used to improve the efficiency of the enzyme reaction, reduce the processing time and enhance the physicochemical properties and cooking quality of brown rice to a greater extent.
The development of paediatric formulations involves an urgent need but also presents many difficulties, e.g. the safety data of existing and new excipients in children stay restrictive; the development of palatable formulations for better compliance is requisite and challenging; the appropriateness of dosage form faces to dysphagia issue and flexibility of dosing for a large range of age. The aim of this work was (i) to develop a taste-masking formulation of a model drug (acetaminophen) on the one hand, and (ii) to elaborate a process for manufacture of fast disintegrating minigranules on the other hand. Sodium caseinate and lecithin, potentially tolerable and safe excipients for paediatric use, were utilized in order to encapsulate the drug through spray-drying. Taste-masking effect was demonstrated by in vitro drug release study and electronic tongue analysis. The characterization of spray-dried particles showed a difference in the surface composition according to the sodium caseinate/lecithin ratio, which related to the taste-masking efficiency. A study was subsequently undertaken to evaluate the effect of process and formulation parameters on the taste-masking efficiency. A full factorial design allowed screening for the most important variables that affect the released amount of drug during the early minutes, i.e. quantity of sodium caseinate and lecithin. An optimized formulation was successfully achieved by simplex design that released the drug 7-fold less than the unmasked drug during the first two minutes. Another approach to improve the taste-masking effect included the use of calcium caseinate rather than sodium caseinate. Calcium caseinate was showed to be more effective in delaying the drug release to a higher extent in association with lecithin. Indeed, the lower the released amount, the better the taste-masking. A multiparticulate dosage form of fast disintegration was developed through extrusion-spheronization followed by freeze-drying. The pellets exhibited suitable quality, e.g. good sphericity, low friability, ability of high drug loading, and moreover, almost immediately disintegrated in contact with water during measurement of disintegration by texture analyzer. This type of pellets promises age-appropriate dosage form for pediatric population thank to facility of administration and flexibility of dosing.
Tablet disintegration characterisation is used in pharmaceutical research, development, and quality control. Standard methods used to characterise tablet disintegration are often dependent on visual observation in measurement of disintegration times. This presents a challenge for disintegration studies of tablets in opaque, physiologically relevant media that could be useful for tablet formulation optimisation. In this study is explored an application of texture analysis disintegration testing, a non-visual, quantitative means of determining tablet disintegration end point, by analysing the disintegration behaviour of two tablet formulations in opaque media. In this study, the disintegration behaviour of one tablet formulation manufactured in-house, and Sybedia Flashtab placebo tablets in water, bovine, and human milk were characterised. A novel method is presented to characterise the disintegration process and to quantify the disintegration end points of the tablets in various media using load data generated by a texture analyser probe. The disintegration times in the different media were found to be statistically different (P<0.0001) from one another for both tablet formulations using one-way ANOVA. Using the Tukey post-hoc test, the Flashtab placebo tablets were found not to have statistically significant disintegration times from each other in human versus bovine milk (adjusted P value 0.1685).
Copyright © 2015. Published by Elsevier B.V.
A big problem in use of chewing gum is the fact that after use, the chewing gum is often not disposed of in an environmentally compatible manner in waste bins or waste paper baskets,but is carelessly disposed of in the manner binds to dust on account of its stickness,become stained black and forms black spots.The syenthetic polymer based chewing gum do not decompose significantly under normal climatic condition and cannot be removed using street clearing methods.A long felt need has existed ,therefore either to modify chewing gum base,in such a manner that they become more easily removed or to modify chewing gum base in such a manner that they are chemically degradable. Corn zein as a gum base offers nonadhesive and biodegradable property.Various plastisizer are used for formulation of corn zein gum. The study shows corn zein is best suited to be used as biodegadable gum base which can be developed as acceptable product for consumers.
The purpose of this study was to develop a physicomechanically customizable oral metal chelatory in situ hot melt dispersion mini-pellet entity which could be utilized within a binary drug delivery system. Avicel(®) RC/CL type R-591 was included within the in situ hot melt dispersion mini-pellet formulations to determine the physicomechanical effect this compound would have on the mini-pellet formulations. The physicomechanical properties of the hot melt in situ mini-pellet formulations were mathematically fitting to regression curves. Physicomechanical adjustment of the in situ hot melt dispersion mini-pellet formulations could be mathematically predicted with the derived regression curve equations. The addition of Avicel(®) RC/CL type R-591 increased the physicomechanical properties such as matrix hardness and increased total disintegration of the in situ hot melt dispersion mini-pellet formulations. The utilization of a physicomechanically customizable oral metal chelatory in situ hot melt dispersion mini-pellet entity within a binary drug delivery system would to achieve a synergistically enhance the activity of a drug-carrying entity or a permeation enhancing entity within a single drug delivery unit. The experimental results indicated that weights of the pellets that achieved optimal hardness ranged between 35 and 45 mg. The melt-dispersion formulations disintegrated within shorter time periods and maintained higher ethylenediaminetetraacetic acid (EDTA) concentrations whereas melt-dispersion formulations which included Avicel(®) had superior physicomechanical properties. Disintegration times ranged between 1,000 s for melt-dispersions containing EDTA and methyloxy polyethylene glycol 2000 (mPEG) only, to >6,000 s for melt-dispersions comprising EDTA, mPEG, and Avicel(®).
Purpose:
To overcome the limitation of insufficient hardness during the production of rapidly disintegrating orally dispersible tablets (ODTs). Furthermore, we investigated the properties and usefulness of functionalized calcium carbonate (FCC) as a new pharmaceutical excipient for the production of ODTs.
Methods:
A highly sensitive tensiometer-based method was developed to measure kinetics of weight loss during tablet disintegration. With this method we were able to determine the residence time of tablets placed on a basket immersed into a test medium. The shapes of tensiometer plots allowed us to categorize substances into four different types of disintegration.
Results:
At the same volume and hardness, the tablet formulations with FCC showed a significantly higher porosity (over 60%) than all other formulations. Residence time depended mainly on the tablet composition rather than on porosity. When combined with disintegrants, FCC formulations exhibited favorable disintegration properties, comparable to those of the marketed drug risperidone oro (disintegration time ca. 10 s).
Conclusions:
Oral dosage forms--based on the new pharmaceutical excipient FCC--can be designed to have a short disintegration time combined with good mechanical strength. Due to these properties, FCC can be used for the preparation of ODTs.
The demand for fast-melting tablets (FMTs) has been growing during the last decade, particularly for children and the elderly who have difficulty swallowing tablets and capsules. These dosage forms are placed in the mouth, allowed to disperse/dissolve in the saliva and then swallowed without the need for water. The advantage of this convenient administration has encouraged both academia and industry to generate new fast-disintegrating formulations and technological approaches in this field. This article reviews the latest progress in the development of FMTs.
Fast-dissolve drug delivery is a rapidly growing area in the pharmaceutical industry. This paper defines the technology, discusses its benefits, and reviews and compares various fast-dissolve technologies currently available on the market.
Rapidly Dissolving Robust Dosage Form
- R Khankari
- J Hontz
- S Chastain
- L Katzner
- R Khankari
- J Hontz
- S Chastain
- L Katzner
to Cima Labs. Inc.) Effervescent Dosage Form with Microparticles
- F Wehling
- S Schuele
- N Madamala
- F Wehling
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