Preparation and Characterization of Metformin Hydrochloride — Compritol 888 ATO Solid Dispersion

Metformin hydrochloride (MET) sustained-release solid dispersions (SD) were prepared by the solvent evaporation and closed melt method, using compritol 888 ATO as the polymer with five different drug-carrier ratios. Characterization of solid dispersion was carried out by Fourier Transform Infrared (FTIR) spectroscopy, ultraviolet (UV) spectroscopy, Differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD). The FTIR and UV studies suggested that no bond formation had occurred between the polymer and the drug. DSC and XPRD results ruled out any interaction or complex formation between the drug and the polymer. The formulated SD had acceptable physicochemical characters and SD with a 1 : 4 drug : Polymer ratio, which released the drug over an extended period of eight-to-ten hours. The data obtained from the in vitro release studies were fitted with various kinetic models and were found to follow the Korsmeyer-Peppas equation. The prepared SD showed good stability over the studied time period. The solvent evaporation method was found to be more helpful than the closed melt method, giving the sustained release action. The SD with a 1 : 4 ratio of drug to polymer, by the solvent evaporation method, was selected as the most effective candidate for the subsequent development of a well-timed, sustained-release dosage form of the drug

Formulation and in vitro evaluation of taste-masked oro-dispersible dosage form of diltiazem hydrochloride

Diltiazem hydrochloride is a calcium channel blocker generally indicated for the treatment of angina and hypertension, and it is extensively metabolized due to the hepatic metabolism. Formulation of diltiazem hydrochloride into an oro-dispersible dosage form can provide fast relief with higher bioavailability. The bitter taste of the drug should be masked to formulate it in a palatable form. In the present work, an attempt was made to mask the taste by complexation technique, with a formulation into an oro-dispersible dosage form, using superdisintegrants Doshion P544, crospovidone (CP) and sodium starch glycolate (SSG). The complexes of diltiazem hydrochloride with β-CD (1:1 molar ratio) were prepared by kneading, co-evaporation, co-grounding, freeze-drying and melting methods. Phase solubility showed stability constant 819.13M-1. Prepared inclusion complexes were evaluated for taste masking and characterized by I.R, XRD, DSC. Using the drug β-CD complex, oro-dispersible tablets were prepared and evaluated for hardness, friability, weight variation, thickness, disintegrating time (DT), dissolution rate and taste. Formulations with 4 % Doshion, 8 % CP and 4 % SSG showed DT of 0.54, 0.35 and 1.23 minutes, respectively.O cloridrato de diltiazem é bloqueador do canal de cálcio geralmente indicado para o tratamento de angina e de hipertensão e é extensamente biotransformado devido ao metabolismo hepático. A formulação do cloridrato de diltiazem em orodispersão pode prover rápida liberação com maior biodisponibilidade. O sabor amargo do fármaco deve ser mascarado para ser formulado em forma palatável. No presente trabalho tentou-se mascarar o sabor pela técnica de complexação, com uma orodispersão, usando superdesintegrantes, como Doshio P544, crospivodina (CP) e glicolato de amido sódico (SSG). Os complexos de cloridrato de diltiazem com β-CD (razão molar 1:1) foram preparados por mistura, coevaporação, comoagem, liofilização e métodos de fusão. A solubilidade de fase mostrou estabilidade constante de 819,13 M-1. Os complexos de inclusão preparados foram avaliados com relação ao mascaramento do sabor e caracterizados por IV, Difração de Raios X e DSC. Empregando-se o fármaco complexado com β-CD, prepararam-se comprimidos dispersíveis e avaliaram-se os mesmos quanto à dureza, friabilidade, variação de peso, espessura, tempo de desintegração (DT), taxa de dissolução e sabor. Formulações com 4% de Doshion, 8% de CP e 4% de SSG mostraram DT de 0,54, 0,35 e 1,23 minutos, respectivamente