Technological development of hard capsules of sertraline hydrochloride

Fast release capsules, containing sertraline hydrochloride, pregelatinized maize starch and microcrystalline cellulose were formulated. For this purpose, different technological assays were elaborated being the formulation 2 selected as the better technological variant. Dry powders were filled into hard gelatin capsules. From this formulation were derived capsules with satisfactory technological properties. The quantification of sertraline through HPLC UV detection method was validated for accuracy, precision, linearity and selectivity. The method was linear over the concentration range 0.5 to 0.75 mg/mL and was shown to be highly reproducible. It could be used, without any interference of capsule excipients, for determination of sertraline from solid dosage form. Hard capsules showed an adequate stability during 24 months demonstrating the feasibility from the process of production of this formulation. Parameters, f1 and f2, were used to confirm similarity of dissolution, in deaerated distilled water, of test formulation and capsules of Prosertin as reference product.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Development and optimization of a novel sustained-release dextran tablet formulation for propranolol hydrochloride

A novel oral controlled delivery system for propranolol hydrochloride (PPL) was developed and optimized. The in vitro dissolution profiles of sustained-release matrix tablets of racemic PPL were determined and compared with the United States Pharmacopeia (USP) tolerance specifications for Propranolol Hydrochloride Extended-Release Capsules. The influence of matrix forming agents (native dextran, hydroxypropyl methylcellulose (HPMC), cetyl alcohol) and binary mixtures of them on PPL release in vitro was investigated. A central composite design was applied to the optimization of a sustained-release tablet formulation. The sustained-release matrix tablets with good physical, mechanical and technological properties were obtained with a matrix excipient:PPL ratio of 60:40 (w/w), with a dextran:HPMC ratio of 4:1 (w/w) and with a cetyl alcohol amount of 15% (w/w). A comparative kinetic study of the present matrix tablets and commercial SUMIAL RETARD capsules (Spain) was established. The value for the similarity factor (f2 = 69.6) suggested that the dissolution profile of the present two sustained-release oral dosage forms are similar. Higuchi (diffusion) and Hixon–Crowell (erosion) kinetic profiles were achieved and this codependent mechanism of drug release was established

Estimation of the percolation thresholds in ternary lobenzarit disodium–dextran–HPMC hydrophilic matrices tablets: Effects of initial porosity

International audienceThe aim of this work is to estimate the excipient percolation threshold for a new combined matrix native dextran (DT), series B110-1-2 (Mw 2×106): HPMC K4M CR: lobenzarit disodium (LBD) system and demonstrate the advantages of this ternary system with respect to previously reported binary dextran:LBD and HPMC:LBD tablets. The formulations studied were prepared with different amounts of excipient (DT:HPMC, 4:1 (wt/wt) for all tablets and relative polymer/drug particle size of 4.17) in the range of 10–70% (wt/wt). Dissolution studies were carried out using the paddle method (100rpm) and one face water uptake measurements were performed using a modified Enslin apparatus. The Higuchi's models as well as the non-linear regression were employed as empiric methods to study the released data. Values of diffusion exponent 0.588<n<0.784 (Korsmeyer equation) for dissolution profile and water uptake mechanism 0.715<n<0.960 (Davidson and Peppas equation) suggests anomalous or complex mechanisms in all cases. The critical points in ternary tablets were reduced from 44.75% (v/v) of excipient (correspond to purely native dextran) to 22.34% (v/v) (corresponding to mixture native dextran:HPMC, 4:1, wt/wt). The initial porosity (IP) of hydrophilic matrices above the values of 20% has an important influence on the percolation threshold as well as on establishment of the gel barrier responsible for the controlled release from the DT:HPMC:LBD tablets

Development of a lisinopril (5 mg) formulation

Se describe el desarrollo de diferentes variantes tecnológicas de tabletas de Lisinopril (5 mg de dosis). Se evaluó el efecto de diferentes excipientes sobre la calidad tecnológica de los comprimidos a partir de un diseño de experimento 22. Se describe un estudio comparativo de dos procedimientos de elaboración: compresión directa y granulación húmeda. El estudio demostró que es factible la elaboración de este producto por ambos métodos.Development of different formulations of lisinopril (5 mg) is described. Factorial experimental design (22) was employed in order to evaluate the effect of different excipients on the quality of tablets. A comparative study for two manufactured process is described. Obtained results show that direct compression and wet granulation process can be used for development of Lisinopril 5 mg tablets.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Development of a lisinopril (5 mg) formulation

Se describe el desarrollo de diferentes variantes tecnológicas de tabletas de Lisinopril (5 mg de dosis). Se evaluó el efecto de diferentes excipientes sobre la calidad tecnológica de los comprimidos a partir de un diseño de experimento 22. Se describe un estudio comparativo de dos procedimientos de elaboración: compresión directa y granulación húmeda. El estudio demostró que es factible la elaboración de este producto por ambos métodos.Development of different formulations of lisinopril (5 mg) is described. Factorial experimental design (22) was employed in order to evaluate the effect of different excipients on the quality of tablets. A comparative study for two manufactured process is described. Obtained results show that direct compression and wet granulation process can be used for development of Lisinopril 5 mg tablets.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Valoración farmacéutica de la dextrana nativa cubana B-110-1-2 obtenida de la caña de azúcar para su empleo en matrices combinadas de liberación controlada

Le dextran est un polysaccharide neutre d origine naturelle, économique, biodégradable et non toxique. Il possède un avantage du point de vue économique par rapport à d autres produits synthétiques : il provient d une source naturelle et renouvelable, ce qui le fait être biocompatible et avoir un nombre remarquable de propriétés physiques et chimiques. De même, par ses qualités de fonctionnalité, il constitue un produit remarquable pour différentes applications pharmaceutiques, notamment dans la formulation de systèmes à libération contrôlée des principes actifs. L objectif principal de cette Thèse est de faire une évaluation du point de vue pharmaceutique du Dextran B-110-1-2 obtenu à partir de la canne à sucre d origine cubaine, ainsi et de son potentiel emploi comme excipient fonctionnel dans la composition des médicaments. La caractérisation du Dextran, ainsi qu une étude comparative avec le dextran commercial B512-F, obtenu à partir de la souche de Leuconostoc mesenteroides ont été développées. Cette étude a démontré la similarité des deux produits du point de vue des qualités physiques, chimiques et pharmacocinétiques. On a démontré que les dextrans natifs avec une moyenne de masse molaire supérieure à 2 x 106 servent au développement de matrices à libération contrôlée, tandis que les fractions de masse molaire entre 40 000 et 170 000 sont les plus appropriés pour la fabrication des comprimés oraux à libération conventionnelle. On a développé un nouveau système de matrice qui combine le dextran natif, avec de l hydroxyprpylméthyl cellulose (HPMC) et de l alcool cétylique, qui permet la libération contrôlée de principes actifs solubles dans l eau sur une période de 24 heures. Les profils de dissolution in vitro des différents médicaments modèles (le chlorhydrate de propanolol et le lobenzarite disodique) ont été étudiés, et les mécanismes qui régissent le phénomène de libération depuis la matrice combinée ont été établis au moyen de modèles mathématiques cinétiques.Dans le but de faciliter la compréhension de ces mécanismes si complexes, les différentes qualités des comprimés, telles que la texture, l augmentation du volume (gonflement), et l érosion ont été analysées. Par application de la théorie de la percolation, les différentes expérimentations conduites pour une optimisation des formulations, il a été démontré que les formules développées présentent une similarité de comportement par rapport aux produits commercialés sur le marché international. Il a par ailleurs été réalisée une transpositiond échelle pilote de ces systèmes thérapeutiques innovants. Les comprimés hydrophiles ont été enrobés en phase aqueuse. Dans les conditions expérimentales développées, les systèmes analysés, protégés de l humidité, ont montré une stabilité et une efficacité de la libération des actifs modèles sur une période de 24 heures.MONTPELLIER-BU Pharmacie (341722105) / SudocSudocFranceF

Estimation of the percolation thresholds in lobenzarit disodium native dextran matrix tablets

The objective of the present work is to estimate for the first time the percolation threshold of a new series of dextran (native dextran of high molecular weight [B110-1-2, Mw=2×106]), in matrices of lobenzarit disodium (LBD) and to apply the obtained result to the design of hydrophilic matrices for the controlled delivery of this drug. The formulations studied were prepared with different amounts of excipient in the range of 20% to 70% wt/wt. Dissolution studies were performed using the paddle method (100 rpm) and one face water uptake measurements were performed using a modified Enslin apparatus. The Higuchi, zero-order, and Hixson-Crowell models as well as the nonlinear regression model were employed as empiric methods to study the release data. Values of diffusion exponent 0.563<n<0.786 (Korsmeyer equation) for dissolution profile and water uptake mechanism 0.715<n<1 (Davidson and Peppas equation) suggested anomalous or complex mechanisms. On the other hand, the contribution of the relaxation or erosion and of the diffusive mechanism in Peppas-Sahlin equation indicated that the main mechanism for drug delivery from tablets is swelling controlled delivery (Kr/Kd<1). The critical points observed in kinetic parameters above 58.63% vol/vol of native dextran B110-1-2 plus initial porosity in the LBD-dextran matrices with a relative polymer/drug particle size of 4.17 were attributed to the existence of an excipient percolation threshold