Experimental design approach for development of novel microemulsion system and immediate release self microemulsifying tablet of nebivolol HCl

The objective of this study was to determine specific combination of pharmaceutical excipients that lead to formulation of efficient nebivolol hydrochloride SMEDDS and its subsequent formulation into IR-SET (Immediate release- Self emulsifying tablet) which will enhance its solubility and dissolution. Solubility and Pseudo-ternary phase studies were carried out to identify the excipients showing highest solubility and to identify the zone of microemulsion with selected ingredients. Liquid-SMEDDS (L-SMEDDS) were optimized for Concentration of oil(X1) and Smix(X2) and formulated using a combination of Kollisolv GTA as oil, Tween 80 as surfactant and propylene glycol as co-surfactant which gave smaller droplet size(Y1) 55.98nm , Emulsification time (Y2) 16±1.5 s,% transmittance (Y3) 99.94±0.47%. Neusilin US2 was used as solid carrier for solidification of L-SMEDDS in to Solid-SMEDDS (S-SMEDDS) by adsorption technique. IR-SET of nebivolol were formulated with S-SMEDDS and optimized for the concentration of binder (X1) (PVP K30) and superdisintegrant (X2) (KOLLIDON CL) which showed low Disintegration time (Y1) (92±0.5s) and low Friability(Y2)(0.424±0.03%). Also the DSC and XRD data revealed the molecular state of the drug in S-SMEDDS. The extent of in-vivo drug release and ex-vivo diffusion values from L-SMEDDS and IR-SET was much higher than pure drug and marketed tablet. In conclusion, the results showed potential of SMEDDS to improve solubility and thus the bioavailability.

Transdermal iontophoretic delivery of timolol maleate

Transdermal iontophoresis would be a promising method for the systemic delivery of water soluble and ionic drugs of relatively high molecular size, including peptides. The objective of the present study was to investigate the effect of biological variable such as guinea pig and human cadaver skin and other variables like drug concentration, current density on the transdermal iontophoretic transport of timolol maleate. The permeation profile of drug using solution and gel formulation was studied and compared. For better bioavailability, better patient compliance, and enhanced delivery, an iontophoretic drug delivery system of a timolol maleate matrix gel was formulated using Carbopol 974P. The study was conducted using silver-silver chloride electrodes across the guinea pig and human cadaver skin. Viscosity measurements and flux calculations indicated the suitability of the Carbopol 974P gel for transdermal iontophoretic delivery of timolol maleate. Anodal iontophoresis with silver-silver chloride electrode significantly increased the timolol maleate skin permeation as compared with the passive permeation study. The amount of timolol maleate transported during iontophoresis was significantly different among the different skins. However, iontophoretic gel formulations provided required flux of drug through human cadaver skin.

A iontoforese transdérmica seria um método promissor para a liberação sistêmica de fármacos solúveis em água e iônicos de relativamente elevado tamanho molecular, incluindo peptídeos. O objetivo do presente estudo foi investigar o efeito da variável biológica, tais como cobaia e pele de cadáver humano, e outras variáveis como concentração do fármaco, densidade de corrente sobre o transporte transdérmico iontoforético de maleato de timolol. Comparou-se o perfil de permeação do fármaco usando a formulação de solução e de gel. Para melhor biodisponibilidade, melhor adesão do paciente e liberação aprimorada, formulou-se sistema de liberação iontoforética gel de maleato de timolol usando Carbopol 974P. O estudo foi conduzido usando eletrodos de prata-cloreto de prata na cobaia e na pele de cadáver humano. Medidas de viscosidade e de fluxo indicaram a adequação do gel Carbopol 974 P para liberação iontoforética transdérmica do maleato de timolol. A iontoforese anódica com eletrodo de prata-cloreto de prata aumentou significativamente a permeação dérmica do maleato de timolol, comparativamente à permeação passiva. A quantidade de maleato de timolol transportado durante a iontoforese foi significativamente diferente entre as diferentes peles . No entanto, as formulações iontoforéticas de gel forneceram o fluxo necessário do fármaco através da pele de cadáver humano.