A REVIEW ON ADVANCES IN PHARMACEUTICAL CO-CRYSTAL PREPARATION ROUTES, INTELLECTUAL PROPERTY PERSPECTIVE AND REGULATORY ASPECTS

As in recent years, due to the pervasiveness of poorly soluble APIs that demonstrates poor and erratic bioavailability, pharmaceutical cocrystal’s applicability to tailor the physicochemical properties has gained attention. Pharmaceutical cocrystal has been an exciting field of interest to researchers as this encouraged several regulatory bodies to create regulatory standards, which led to the approval of these crystals for marketing in various nations. With the upsurge in the growth of pharmaceutical cocrystals, the major concern is over the intellectual property perspective and regulatory status of cocrystals. With the new guidelines from the United States Food and Drug Administration (USFDA) and European Medicines Agency (EMA), the manufacturing and characterization of cocrystal have become less complicated. In this article, various preparation routes are mentioned along with this intellectual property perspective and regulatory perspective, including regulatory guidelines, which give an idea of whether cocrystals meet the criteria for patent eligibility and how they would change the current state of the pharmaceutical industry. Here, we also reviewed some recently approved patients on pharmaceutical crystals, which provided benefits over poor physicochemical property of drug substances and also enhanced the therapeutic effectiveness of that drugs

Formulation and evaluation of biphasic release tablet containing diclofenac beads

The purpose of the present research work was to produce a biphasic delivery system for Diclofenac sodium. A dual component tablet made up of a sustained release beads and immediate release tablet coat was prepared by direct compression using super disintegrating agent. Both the beads and coat contained a model drug (diclofenac sodium). The sustained release effect was achieved with polymers chitosan and sodium alginate. The in vitro release profile from these tablets showed the desired biphasic behavior, the diclofenac contained in the fast releasing component was dissolved within 15 min, whereas the drug in the beads was released upto 8 h.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Green synthesis and anxiolytic activity of some new dibenz-[1,4] diazepine-1-one analogues

AbstractA facile, green approach for the synthesis of some new dibenz[1,4]-diazepine-1-one by a three component reaction of Diamine, 1,3 diketone and aromatic aldehyde using oxalic acid as catalyst in water is described. The products are formed in good yields (92–94%). Newly synthesized dibenz [1,4]-diazepine-1-one analogues were evaluated for the anxiolytic activity by the elevated plus maze method. From the activity data it is observed that compounds, 4g, 4h and 4k show promising anxiolytic activity

Development and validation of RP-HPLC method for determination of Atorvastatin calcium and Nicotinic acid in combined tablet dosage form

A simple, specific and accurate reverse phase liquid chromatographic method was developed for the simultaneous determination of Atorvastatin calcium and Nicotinic acid in tablet dosage forms. The analysis has been performed by using Agilent ZORBAX SB-C18 (150 × 4.6 mm, 3.5 u) and mobile phase containing acetonitrile: distilled water (85:15) at pH 4.5 (adjusted with phosphoric acid). The detection was carried out at 261 nm with a flow rate of 1.0 ml/min. The retention times of Atorvastatin calcium and Nicotinic acid were 6.092 and 3.125 min, respectively. The method was validated according to ICH guidelines. The method was validated for specificity, precision, linearity, accuracy and robustness. The linearity for Atorvastatin calcium and Nicotinic acid were in the range of 2–12 and 10–80 μg/ml respectively. The recoveries of Atorvastatin calcium and Nicotinic acid were found to be in the range of 99.031% and 99.744% respectively. The proposed method was validated and successfully applied to the estimation of Atorvastatin calcium and Nicotinic acid in combined tablet formulation

Dissolution rate enhancement of fenofibrate using liquisolid tablet technique

Fenofibrate is more effective drug as compared to other fibrates. But low bioavailability of it is due to its poor aqueous solubility. The purpose of present study was to improve fenofibrate dissolution through its formulation into liquisolid tablets and then to investigate in vitro performance of prepared liquisolid systems. By use of this technique, liquid medications such as solutions or suspensions of water insoluble drugs in suitable non-volatile liquid vehicles can be easily converted into powders with acceptable flow properties and compression behavior by using suitable powder excipients. X-ray powder diffraction and Differential Scanning Calorimetry were used for evaluation of physicochemical properties of Fenofibrate in liquisolid tablets. Stereomicroscopy was used to assess morphological characteristics of liquisolid formulation. Enhanced drug release profiles due to increased wetting properties and surface of drug available for dissolution was obtained in case of liquisolid tablets.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Dissolution rate enhancement of fenofibrate using liquisolid tablet technique : Part II: evaluation of in vitro dissolution profile comparison methods

The present work deals with the comparison of in vitro dissolution profiles of fenofibrate liquisolid tablet formulations with those of marketed fenofibrate tablets, and the application of statistical methods to evaluate each method for its usefulness. The methods used to study dissolution profile comparison include Model independent method (Similarity factor, f2); Model dependent methods (Zero order, First order, Hixson-Crowell, Matrix, Peppas, Higuchi models) and statistical methods based on ANOVA. Model independent method was found to be easier and simple to interpret. The f2 value relates closeness of dissolution profiles. Dissolution profile followed Peppas model as "best fit" model. The application and evaluation of model dependent methods are more complicated. These methods give acceptable model approach which is indication of true relationship between percent drug release and time variables, including statistical assumptions. Statistical approach is very simple and is more discriminative of dissolution profiles. The liquisolid formulation of fenofibrate serves to be an effective way to enhance dissolution rate of fenofibrateColegio de Farmacéuticos de la Provincia de Buenos Aire

Dissolution Rate Enhancement of Fenofibrate Using Liquisolid Tablet Technique. Part II: Evaluation of In Vitro Dissolution Profile Comparison Methods

SUMMARY. The present work deals with the comparison of in vitro dissolution profiles of fenofibrate liquisolid tablet formulations with those of marketed fenofibrate tablets, and the application of statistical methods to evaluate each method for its usefulness. The methods used to study dissolution profile comparison include Model independent method (Similarity factor, f 2 ); Model dependent methods (Zero order, First order, Hixson-Crowell, Matrix, Peppas, Higuchi models) and statistical methods based on ANOVA. Model independent method was found to be easier and simple to interpret. The f 2 value relates closeness of dissolution profiles. Dissolution profile followed Peppas model as "best fit" model. The application and evaluation of model dependent methods are more complicated. These methods give acceptable model approach which is indication of true relationship between percent drug release and time variables, including statistical assumptions. Statistical approach is very simple and is more discriminative of dissolution profiles. The liquisolid formulation of fenofibrate serves to be an effective way to enhance dissolution rate of fenofibrate