Evaluation and comparison of dissolution data derived from different modified release dosage forms: An alternative method

Temple University, School of Pharmacy, Department of Pharmaceutical Sciences, 3307 North Broad Street, Philadelphia, PA 19140, USA.
Journal of Controlled Release (Impact Factor: 7.71). 11/1998; 55(1):45-55. DOI: 10.1016/S0168-3659(98)00022-4
Source: PubMed


Dissolution testing is an essential requirement for the development, establishment of in vitro dissolution and in vivo performance (IVIVR), registration and quality control of solid oral dosage forms. The objective of the present study was to investigate the effect of delivery system positioning in accordance with the USP 23-recommended dissolution methods and the proposed modification on drug release from controlled release systems having different operating release mechanisms, namely, swellable floatable, swellable sticking and osmotic pump. The delivery systems were evaluated by placing each dosage form either in the dissolution vessel in accordance with the USP 23 methods or over/below a designed ring/mesh device for achieving full surface exposure to the dissolution medium for sticking or floatable systems respectively. Results indicate that the overall release profiles from the sticking and floatable systems of theophylline are sensitive to their positioning in the dissolution vessel (P<0.05). Furthermore, release of diltiazem hydrochloride from the sticking system also demonstrated sensitivity (P<0.05). In contrast, the floatable dosage form of this latter drug with the application of a helical wire sinker, or when it was placed below the ring/mesh assembly, or by allowing the dosage form to float, did not show sensitivity (P>0.05) for the overall release behavior. This was attributed to the greater solubility of diltiazem hydrochloride (50% solubility in water at 25 degreesC) in comparison to theophylline which is a sparingly soluble drug (0.85% solubility in water at 25 degreesC). Drug release from the osmotic pump appeared to be identical under the given experimental conditions (P>0.05). Statistical analysis of data was performed by comparing the t50%, t70%, t90%; mean dissolution times (MDT50%, MDT70%, MDT90%); the "difference factor, f1" and "similarity factor, f2". It is concluded that the results derived from the application of the "similarity factor, f2" are superior to the individual time points (e.g. tx%) and MDTx% values in differentiating between overall release patterns or the border line release profile differences. It also became apparent that in the case of the swellable sticking systems full surface exposure to the dissolution medium results in greater release rate. For the osmotic pump the required osmotic pressure threshold necessary for constant rate drug delivery appears to have reached independent of the hydrodynamic conditions. A successful and more accurate evaluation of dissolution data can be derived when full surface exposure is considered and this can be accomplished by dissolution method modification with the aid of the designed ring/mesh assembly.

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    • "(7) and a modification of the difference factor's formula was used to eliminate the need for defining a reference product in the calculation; this modified difference factor was named [ T D $ I N L I N E ] which was calculated by Eq. (8). In these equations, n is the number of sample, R and T are the percent release of the reference and test products at each time point of j (Costa and Sousa Lobo, 2001; Pillay and Fassihi, 1998). "
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    ABSTRACT: The aim of this study was to produce microparticles with optimal aerodynamic diameter for deep lung delivery (i.e., 1-3μm) of a protein drug intended for systemic absorption, using a combination of generally regarded as safe (GRAS) excipients. Based on the preliminary experiments, mannitol, l-alanine, sodium alginate, chitosan and dipalmitoylphosphatidilcholine (DPPC) were chosen as excipients and human insulin as a model protein drug. Dry powders were prepared by spray-drying. Powders with varying yields (29-80%) and low tapped densities (0.22-0.38g/cm(3)) were obtained. Scanning electron microscopy (SEM) revealed distinctive particle morphologies among formulations from isolated spherical to highly folded particles. Aerodynamic properties were assessed by next generation impactor (NGI). Mass median aerodynamic diameter (MMAD) and fine particle fraction (FPF) ranged between 2.1 and 4.6μm and 46 and 81%, respectively. A comparative study of protein release from microparticles was conducted in vitro using an open membrane system with more than 50% cumulative release in all formulations which followed different kinetic models. Insulin's integrity was investigated by spectrofluorimetry and electrophoresis, and no tangible changes were observed in the structure of insulin. Of the formulations studied, the third, containing mannitol/sodium alginate/insulin/sodium citrate showed promising characteristics, optimal for systemic delivery of proteins via deep lung deposition.
    Full-text · Article · Feb 2014 · International Journal of Pharmaceutics
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    • "All experiments were carried out in triplicate. Similarity factor f 2 (Pillay and Fassihi, 1998; Polli et al., 1997) was introduced to justify the synchronicity of each two of the release profiles, which was defined as: "
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    ABSTRACT: The pharmacological activity of herbal medicines is determined by the active components ratio that defines the medicine. Significant alteration of the components ratio will lead to major changes in the pharmacological activities. In designing sustained or controlled release delivery systems of herbal medicines, we developed the concept of synchronized release which was characterized by keeping active components' initial ratio throughout the whole release process. In this study, this concept was extended by developing a novel synchronized release system based on osmotic release strategy, which was designed as a monolithic osmotic tablet consisting of a tablet core and semi-permeable coating of cellulose acetate with mechanically perforated release orifices. The rationale of synchronized release lies in simultaneous release of silymarin multiple components in a solubilized state through the release orifices. To ensure quick solubilization of multiple components, silymarin was first formulated as fast-release solid dispersion before formulating into the osmotic tablet. The concept of synchronized release was well proved by the results of high similarity of the release profiles of the five active components in silymarin (taxifolin, silychristin, silydianin, silybin and isosilybin). Zero-order release profiles can be maintained up to approximately 20h. High synchronicity and controlled release can be achieved by adjusting the formulation variables. It is indicated that the osmotic release strategy has great potential to achieve synchronized and controlled release of multiple components in herbal medicines.
    Full-text · Article · Dec 2012 · International Journal of Pharmaceutics
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    • "on offers a simple and practical approach to achieve increased gastric residence time for the dosage form and controlled drug release (Cargill et. al., 1988). Dipyridamole (DP) is a poorly water soluble weak base with pKa of 6.4. DP inhibits thrombus formation when given chronically and causes vasodilation when given at high doses over short time (Pillay et. al., 1998). The extent of absorption of dipyridamole was remarkably lower when gastric pH was continuously elevated to 6.0, whereas absorption increased when gastric pH temporarily decreased to 1.8 (Chen et al., 2000, Timmermans et al 1994). So, it would be beneficial to develop floating drug delivery system which prolongs the gastric residence t"
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    ABSTRACT: The present study describes the design and development of buoyant matrices of dipyridamole. The matrices were prepared by direct compression method using simplex lattice design as an optimization technique. Amount of HPMC K4M (X1), sodium bicarbonate (X2) and ethyl cellulose (X3) were used as the independent variables where floating lag time (Y1) and percentage drug release at 6h (Y2) were considered as the response variables. As per the simplex lattice design total 7 formulations were formulated. Matrices were evaluated for physical parameters, in-vitro buoyancy, in-vitro drug release, water uptake studies. Drug release data was fitted into different kinetic models. The results of response variables were statistically evaluated using design expert 8.0 software. Polynomial models were generated for all the response variables using multiple linear regression analysis (MLRA) approach. A statistical model incorporating 7 interactive terms was used to evaluate the responses. The results of response variables are expressed for model analysis by Scheffe's special cubic model. Graphical representation was done by response surface plots and contour plots. The resulted model equation showed that factor X1 responsible for prolongation of drug release. On the basis of acceptance criteria the formulation coded by DP3 was selected as a promising formulation from the simplex lattice batches which fitted best to zero order release kinetic model.
    Full-text · Article · Dec 2012 · Journal of Applied Pharmaceutical Science
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