Mathematical methods for quantification and comparison of dissolution testing data

In recent years, drug release/dissolution from solid dosage forms has been the subject of intense and profitable scientific developments. Whenever a new solid dosage form is developed or produced, it is necessary to ensure that drug dissolutionoccurs in an appropriate manner. The pharmaceutical industry and the registration authorities do focus, nowadays, on drug dissolution studies. The quantitative analysis of the values obtained in dissolution/release tests is easier when mathematicalformulas that express the dissolution results as a function of some of the dosage forms characteristics are used. This work discusses the analysis of data obtained for dissolution profiles under different media pH conditions using mathematical methodsof analysis described by Moore and Flanner. These authors have described difference factor (f1) and similarity factor (f2), which can be used to characterise drug dissolution/release profiles. In this work we have used these formulas for evaluation of dissolution profiles of the conventional tablets in different pH of dissolution medium (range of physiological variations)

Development of ternary solid dispersions with hydrophilic polymer and surface adsorbent for improving dissolution rate of carbamazepine

In this study solid dispersions of carbamazepine in the hydrophilic Kollidon (R) VA64 polymer, adsorbed onto Neusilin (R) UFL2 adsorption carrier have been employed to improve carbamazepine dissolution rate. In order to evaluate effects of changing in the proportions of all solid dispersion components on carbamazepine dissolution rate, D-optimal mixture experimental design was used in the formulation development. From all prepared solid dispersion formulations, significantly faster carbamazepine dissolution was observed compared to pure drug. Ternary solid dispersions containing carbamazepine, Kollidon (R) VA64 and Neusilin (R) UFL2 showed superior dissolution performances over binary ones, containing only carbamazepine and Neusilin (R) UFL2. Proportion of Kollidon (R) VA64 showed the most profound effect on the amount of carbamazepine dissolved after 10 and 30 min, whereby these parameters increase upon increasing in Kollidon (R) VA64 concentrations up to the middle values in the studied range of Kollidon (R) VA64 concentrations. Physicochemical characterization of the selected samples using differential scanning calorimetry, FT-IR spectroscopy, powder X-ray diffraction and polarizing light microscopy showed polymorphic transition of carbamazepine from more thermodynamically stable monoclinic form (form III) to less thermodynamically stable triclinic form (form I) in the case of ternary, but not of binary solid dispersion formulations. This polymorphic transition can be one of the factors responsible for improving of carbamazepine dissolution rate from studied solid dispersions. Ternary solid dispersions prepared with Kollidon (R) VA64 hydrophilic polymer and Neusilin (R) UFL2 adsorption carrier resulted in significantly improvement of carbamazepine dissolution rate, but formation of metastable polymorphic form of carbamazepine requires particular care to be taken in ensuring product long term stability

Recent advances in the identification and prediction of polymorphs

An increased understanding of the phenomenon of polymorphism should enable pharmaceutical scientists to gain control over the crystallization process in order to selectively obtain the desired polymorph or suppress the growth of an undesired one. Phase changes during processing and scale-up are a problem, which may be avoided by carefully designed initial small-scale studies. The availability of detailed structural data, combined with strategic design of substrates and additives, has led to significant advances in the control over the polymorphs obtained in a particular crystallization. With all the information available from these initial studies, it should be possible to design and to select processing conditions which would give a desired polymorph and maintain the desired form throughout the various stages of drug processing and manufacture