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Dissolution profile comparison of FaSSIF vs PM-1 for (a) dipyridamole, (b) glimepiride, and (c) ibuprofen.
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The objective of this study was to employ a tailor-made, surface-active agent (phosphonobile acid) in the design of dissolution media that more closely reflect various luminal fluid physicochemical parameters such as buffer capacity, osmolarity, surface tension, and pH. The proposed media are simple to prepare and use, and thus can be explored for...
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... in vitro drug release profiles obtained for the three drugs in PM-1 were compared with FaSSIF, and those obtained using PM-2 were compared with FeSSIF. The results are tabulated in Table 3 and graphically represented in Figures 3 and 4. The f 2 values obtained from the comparison of dissolu- tion profiles of the three BCS II drugs in PM-1 and PM-2 versus reported media (FaSSIF and FeSSIF) were nearly all greater than 50, indicating similarity between the pro- posed and reported media in terms of drug release. ...
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The rate-limiting step to drug absorption is often dissolution from the dosage form, especially for poorly soluble compounds. Two possibilities for improving the dissolution of these drugs are to increase the available surface area and to improve their apparent solubilities under physiologically relevant conditions with surfactants as wetting agent...
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... The filtrates were analyzed for drug content. The test was performed in triplicate [10,11]. ...
Convenience of administration and patient compliance are gaining significant importance in the design of dosage forms. Glibenclamide is an orally administered antihyperglycemic agent, used in the management of non-insulindependant (type-2) diabetes mellitus. Difficulty in swallowing (dysphagia) is common among all age groups, especially in elderly and pediatrics. Persons suffering from dysphagia may get choked when they consume liquid formulations, thus to alleviate such problem liquid formulation of high viscosity were prepared. Formulation of oral soft gel (batches of Glibenclamide) were prepared by using hydrophilic polymer guar gum at concentration ranging from 0.3-0.5% w/v and pectin at two different concentrations (0.2% and 0.3% w/v). The batch with 0.5% w/v guar gum and 0.2%w/v pectin not only showed 85% drug release after 1h. The prepared batches were evaluated for appearance, viscosity, pH, drug content, syneresis and in vitro drug release. The optimized batch showed substantial stability when subjected to short term stability study (0-8°C and at room temperature). The problem of dose measurement by patients was outweighed as oral medicated gels are to be packed in unit dose container. Keywords: Diabetes mellitus, Jelly, Dysphagia, Glibenclamide
... The class II category, low solubility and high permeability drugs are identified as potential drug candidates for investigation. The low solubility aspects can be handled in order to develop a biorelevant and discriminating method for dissolution [9][10][11][12][13] . The development of a meaningful dissolution procedure for drug products with limited water solubility has been a challenge to both the pharmaceutical industry and the agencies that regulate them [14] . ...
The establishment of biorelevant and discriminating dissolution procedure for drug products with limited water solubility is a useful technique for qualitative forecasting of the in vivo behavior of formulations. It also characterizes the drug product performance in pharmaceutical development. Lornoxicam, a BCS class-II drug is a nonsteroidal antiinflammatory drug of the oxicam class, has no official dissolution media available in the literature. The objective of present work was to develop and validate a discriminating and biorelevant dissolution test for lornoxicam tablet dosage forms. To quantify the lornoxicam in dissolution samples, UV spectrophotometric method was developed using 0.01M sodium hydroxide solution as solvent at λma×376 nm. After evaluation of saturation solubility, dissolution, sink conditions and stability of lornoxicam bulk drug in different pH solutions and biorelevant media, the dissolution method was optimized using USP paddle type apparatus at 50 rpm rotation speed and 500 ml simulated intestinal fluid as discriminating and biorelevant dissolution medium. The similarity factor (f2) were investigated for formulations with changes in composition and manufacturing variations, values revealed that dissolution method having discriminating power and method was validated as per standard guidelines. The proposed dissolution method can be effectively applied for routine quality control in vitro dissolution studies of lornoxicam in tablets and helpful to pharmacopoeias.
... This could in turn have an influence on osmolality changes 32 . Osmolality is determined by freezing-point depression using an osmometer, buffer capacity is determined by titration with 1 M hydrochloric acid and surface tension is measured using stalagnomet33 . The dissolved gases can cause changes in the performance of the dissolution medium by changing pH, forming bubbles on the dosage form or altering the interaction of the medium and the API. ...
Dissolution testing is a valuable tool that provides key information about bioavailability or bioequivalency as well as batch to batch consistency of drug. Since the number of poorly soluble drug is increasing, the selection of adequate dissolution test for these becomes more and more important. Biorelevant is a term, used to describe a medium that has same relevance to the in vivo dissolution condition for the compound. The development of biorelevant dissolution medium includes simulation of
gastrointestinal condition, hydrodynamic characteristics, and physicochemical parameters of drug, prediction of plasma profile and lastly the development of IVIVC. Biorelevant dissolution testing designed with appropriate simulated media and hydrodynamics are useful from the early stages of drug discovery and development for identifying the biopharmaceutical performance of compound (i.e. solubility problems, food effects, precipitation in the small intestine) through the later stages of development to assist in formulation strategies and the establishment of IVIVC that will lead to reduction of the number of animal experimentation, bioavailability and bioequivalence studies. The aim of this review article is to provide comprehensive information on the steps that should be considered during developing biorelevant dissolution medium for poorly soluble drugs and the composition of biorelevant dissolution medium to predict in vivo performance more accurately than the compendia dissolution medium.
Keywords: Biorelevant, Simulated gastrointestinal condition, hydrodynamic, IVIVC etc.
... For such drugs, surfactants in various concentrations can be added to improve the condition 13,20 . Bagwe et al. 29 discussed the application of surfactants including SLS as dissolution aid for poorly soluble ingredients for their appropriateness in demonstrating the biological behaviour of drugs in comparison to hydro-alcoholic media 30,31 . For this study phosphate buffer pH 7.4 with different concentrations of SLS (0.1, 0.2, 0.4, 0.8, 1, and 1.2) was prepared as biowaiver dissolution medium to compare the dissolution profile of the drug. ...
Glimepiride is a third generation sulphonylurea antidiabetic drug. It shows low, pH dependent solubility thus is classified as class II drug according to Biopharmaceutics Classification Systems (BCS). The poor solubility of the drug may cause poor dissolution and unpredicted bioavailability. Scientists can ask for biowaivers in case of Class I compounds if they are formulated as immediate release oral dosage forms. Class II drugs are also the candidates for a waiver of bioequivalence and bioavailability studies. In the present study developed dissolution medium was easy to prepare, stable over a longer period, simple and cost-effective. In vitro dissolution test was performed using 2% SLS as the medium of dissolution in USP apparatus II (paddle) at 100 rpm, for glimepiride tablet could reliably discriminate among different products. Drug release was found above 95% within 30 min. To explain the kinetics of released drug contents, various statistical models including First-order, Zero-order Higuchi’s, Hixson-Crowell’s, and Weibull’s were used. Glimepiride was best fitted to the Weibull’s kinetics. Furthermore, goodness-offit test, the mean square error and the Akaike Information Criterion were used for selection of appropriate model; f2 test was applied for comparison of similarity between the release profile of various trial marketed brands. © Latin American Journal of Pharmacy 2014. All Rights Reserved.
... Dissolution testing of poorly soluble compounds in immediate release solid dosage forms presents several challenges. Single dissolution method for the analysis of combined dosage forms is preferred for simplification of quality control testing [7][8][9][10][11][12][13]. However, development of a single dissolution method for DRT and MEF is practically challenging due to the pH dependent dissolution of these two drugs. ...
Purpose: To develop and validate a dissolution test method for tablets containing 80 mg of drotaverine hydrochloride (DRT) and 250 mg of mefenamic acid (MEF). Methods: Sink conditions, drug stability and specificity in different dissolution media were tested to optimize a dissolution test method using a USP paddle type dissolution test apparatus set at a speed of 50 rpm. The dissolution medium consisted of 900 ml of phosphate buffer (pH 6.8) containing 0.25% w/v cetrimide at 37 ± 0.5 o C and 45 min time-point. To determine both drugs simultaneously, a first derivative UV spectrophotometric method was developed and validated. Drug release was analyzed by first derivative UV method at 253.8 nm and 304 nm for DRT and MEF respectively. The dissolution method was validated as per ICH guidelines. Results: The two brands each showed 98% of drug release for both drugs when the developed dissolution method was used. The regression plot was linear in the concentration range 4 -24 µg/mL for each of the drugs and regression coefficient (r 2) was greater than 0.999 for each drug. Relative standard deviation (% RSD) for precision and accuracy of proposed method was < 2. Conclusion: The proposed dissolution method is simple, cost-effective, precise, accurate and specific. It can be successfully employed in routine quality control of DRT and MEF combination tablets.
Introduction. «Dissolution test» for drugs is one of the key studies of control and, in many ways, is designed to simulate the bioavailability of the active substance under the conditions of use. However, there are several drugs containing active pharmaceutical substances that are poorly soluble under standard conditions. For this substances action is local, so, they are practically not absorbed in the human body, but showed the necessary therapeutic effect. This work discusses the development of conditions for «Dissolution test» in lipophilic-based suppositories containing natamycin, which is an antifungal agent related to tetraene macrolides, poorly soluble in water and, therefore, in standard buffer solutions intended for this test.
Aim. Choose the conditions for conducting «Dissolution test», under which it will be possible to achieve complete release of the active substance from lipophilic-based suppositories on «Pimafucin» and «Primacin».
Materials and methods. The objects of the study are lipophilic-based suppositories containing natamycin. The study was carried out using dissolution testers (Rotating Basket and Flow Cell apparatus) and an HPLC system to define the amount of natamycin released.
Results and discussion. The research objects were analyzed under «Dissolution test». The work shows the possibility of conducting a test with complete release of the active substance by adding surfactants and an organic solvent, which is acceptable for quality control dissolution medias.
Conclusion. Conditions for «Dissolution test» have been developed for suppositories containing natamycin.
The recent impact of the Biopharmaceutics Classification System (BCS) and the Biopharmaceutics Drug Disposition Classification System (BDDCS) on relevant scientific advancements is discussed. The major advances associated with the BCS concern the extensive work on dissolution of poorly absorbed BCS class II drugs in nutritional liquids (e.g. milk, peanut oil) and biorelevant media for the accurate prediction of the rate and the extent of oral absorption. The use of physiologically based pharmacokinetic (PBPK) modeling as predictive tool for bioavailability is also presented. Since recent dissolution studies demonstrate that the two mechanisms (diffusion- and reaction-limited dissolution) take place simultaneously, the neglected reaction-limited dissolution models are discussed, regarding the biopharmaceutical classification of drugs. Solubility- and dissolution-enhancing formulation strategies based on the supersaturation principle to enhance the extent of drug absorption, along with the applications of the BDDCS to the understanding of disposition phenomena are reviewed. Finally, recent classification systems relevant either to the BCS or the BDDCS are presented. These include: i) a model independent approach based on %metabolism and the fulfilment (or not) of the current regulatory dissolution criteria, ii) the so called ΑΒΓ system, a continuous version of the BCS, and iii) the so-called Extended Clearance Classification System (ECCS). ECCS uses clearance concepts (physicochemical properties and membrane permeability) to classify compounds and differentiates from BDDCS by bypassing the measure of solubility (based on the assumption that since it inter-correlates with lipophilicity, it is not directly relevant to clearance mechanisms or elimination).
The polyelectrolyte matrix tablets loaded with an oppositely charged drug exhibit complex drug-release mechanisms. In this study, the release mechanism of a cationic drug doxazosin mesylate (DM) from matrix tablets based on an anionic polyelectrolyte λ-carrageenan (λ-CARR) is investigated. The drug release rates from λ-CARR matrices are correlated with binding results based on potentiometric measurements using the DM ion-sensitive membrane electrode and with molecular characteristics of the DM-λ-CARR-complex particles through hydrodynamic size measurements. Experiments are performed in solutions with different ionic strength and with the addition of an anionic surfactant sodium dodecyl sulphate (SDS). It is demonstrated that in addition to swelling and erosion of tablets, the release rates depend strongly on cooperative interactions between DM and λ-CARR. Addition of SDS at concentrations below its critical micelle concentration (CMC) slows down the DM release through hydrophobic binding of SDS to the DM-λ-CARR complex. On the contrary, at concentrations above the CMC SDS pulls DM from the complex by forming mixed micelles with it and thus accelerates the release. Results involving SDS show that the concentration of surfactants that are naturally present in gastrointestinal environment may have a great impact on the drug release process.
Dissolution process is considered as an important in vitro tool for evaluating the bioequivalence of products. Such a method, if properly mimic the in vivo conditions, it would surrogate the in vivo studies. Bioequivalence problems arise in class-II and class-IV categories of Biopharmaceutical Classification of Drugs (BCS). Efavirenz (BCS Class II drug) is used in active anti retroviral therapy. Saturation solubility of efavirenz bulk drug was evaluated in various surfactant media, pH solutions and bio-relevant media. We optimized the dissolution conditions for efavirenz with 900 ml of simulated gastric fluid with 0.25% w/v sodium lauryl sulphate (SGF-0.25% w/v SLS) as discriminating and bio-relevant dissolution medium at 50 rpm for 45 min (5 min time interval) with USP apparatus II. The optimized media contained a less amount of SLS (0.25% w/v) in SGF compared with 1% and 2% SLS concentration stated in the official monographs (IP, BP, USP) and FDA guidelines mimic the GI tract environment.
We studied the dissolution profiles of efavirenz bulk drug and its formulations in various concentrations of SLS alone (0.25% - 2.0% w/v) and with simulated gastric fluid with SLS. In vitro dissolution profiles of efavirenz and its formulations in optimized dissolution media (0.25% w/v SLS with SGF) folIowed zero order kinetics with diffusion mechanism drug release.
