Development and optimization of self microemulsifying drug delivery of domperidone

The present investigation is aimed to develop self-microemulsifying drug delivery system (SMEDDS) to improve the in vitro dissolution of a BCS (Biopharmaceutical Classification System) class II anti emetic agent, domperidone. Solubility study was performed to identify the ingredients showing highest solubility of domperidone. The ternary phase diagrams were plotted for selected components to identify the area of microemulsion existence. D-optimal mixture experimental design was applied to optimize a liquid SMEDDS using formulation variables; the oil phase X1 (Oleic acid), the surfactant X2 (Labrasol) and the co-surfactant X3 (Transcutol HP). The liquid SMEDDS were evaluated for droplet size, emulsification time, % transmittance and drug release. Stability study was performed at 40 °C/75% RH. Liquid formulation was solidified by adsorption on carrier Aerosil 300. Solid SMEDDS was evaluated and compared with liquid SMEDDS and marketed formulation. Oleic acid was selected as oil, Labrasol as surfactant and Transcutol HP as co-surfactant for formulation of SMEDDS. The optimized batch showed best results in terms of smaller droplet size (<170 nm), emulsification time (<40 s) and drug release (>85% in 15 min) and was stable for 3 months. Solid SMEDDS containing Aerosil 300 showed good flow properties and uniform drug content. XRPD study revealed that the crystalline drug was converted to amorphous form in solid SMEDDS. The rate and extent of drug dissolution from solid SMEDDS was significantly higher than pure drug and commercial tablet formulation. The results demonstrate the potential of SMEDDS as a means of improving solubility, dissolution and hence the bioavailability.

O presente estudo teve como objetivo desenvolver sistemas de liberação auto-microemulsificantes (Self-Microemulsifying Drug Delivery System - SMEDDS) de domperidona, agente antiemético, classe II, segundo o sistema de classificação Biofarmacêutica, para melhorar sua dissolução in vitro. Estudo foi realizado para identificar os componentes que revelaram maior solubilidade da domperidona. Determinaram-se os diagramas de fase ternários para esses componentes selecionados tendo em vista a identificação da região de formação da microemulsão. O planejamento experimental foi empregado para otimizar os SMEDDS líquidos, utilizando as seguintes variáveis de formulação: a fase oleosa X1 (ácido oleico), o agente tensoativo X2 (Labrasol) e co-tensoativo X3 (Transcutol HP). Os SMEDDS líquidos foram avaliados quanto às seguintes características: tamanho da gota, tempo de emulsificação,% de transmitância e liberação do fármaco. O estudo de estabilidade foi realizado a 40 °C/75% de umidade relativa. A formulação foi convertida em forma sólida por sua adsorção em Aerosil 300. Os SMEDDS sólidos foram avaliados e comparados com SMEDDS líquidos e a formulação comercializada. O ácido oléico foi selecionado para a fase oleosa, Labrasol como agente tensoativo e Transcutol como co-tensoativo para a formulação de SMEDDS. O lote otimizado mostrou os melhores resultados: menor tamanho de gota (<170 nm), menor tempo de emulsificação (<40 segundos), e de liberação do fármaco (> 85% em 15 min). Além disso, a formulação otimizada manteve-se estável no período de 3 meses. Os SMEDDS sólidos contendo Aerosil 300 apresentaram boas propriedades de fluxo e uniformidade de conteúdo do fármaco. O estudo de difração de raios-X revelou que o fármaco cristalino foi convertido para a forma amorfa, nos SMEDDS sólidos. A velocidade de dissolução do fármaco a partir dos SMEDDS sólidos foi significativamente maior, quando comparado ao fármaco livre e à formulação de comprimidos comercial. Os resultados demonstram o potencial dos SMEDDS como meio para melhorar a solubilidade, a dissolução e, consequentemente, a biodisponibilidade da domperidona.

Effect of biotherapeutics on antitoxin IgG in experimentally induced Clostridium difficile infection.

Purpose: Recurrent diarrhoea after successful treatment of primary Clostridium difficile associated disease (CDAD) occurs due to bowel flora alterations and failure to mount an effective antibody response. Apart from antibiotics, risk factors include immunosuppressive and acid-suppressive drug administration. Biotherapeutics such as probiotic and epidermal growth factor (EGF) may offer potential effective therapy for CDAD. Materials and Methods: The effect of biotherapeutics in mounting an antibody response against C. difficile toxins was studied in BALB/c mice challenged with C. difficile after pre-treatment with ampicillin, lansoprazole or cyclosporin. Sera from sacrificed animals were estimated for antitoxin IgG by enzyme linked immunosorbent assay. Results: Antitoxin IgG was significantly higher (P<0.05) in C. difficile challenged groups compared to unchallenged controls, but insignificant (P>0.05) in animals in which C. difficile was given after pre-treatment with cyclosporin compared to those without any pre-treatment, or pre-treatment with antibiotic or lansoprazole. In inter-subgroup comparisons also significant anomaly in production of antitoxin IgG was found. The antitoxin IgG levels were raised in animals administered C. difficile after pre-treatment with ampicillin, but lower in animals administered cyclosporin. High levels of antitoxin IgG were also found in the serum samples of animals receiving lansoprazole and C. difficile. Conclusions: Probiotics showed their beneficial effect by boosting the immune response as seen by production of antitoxin IgG. Oral administration of EGF did not affect the immune response to C. difficile toxins as significant increase was not observed in the serum antitoxin IgG levels in any of the groups investigated.

Estudios biofarmacéuticos de productos similares de teofilina del mercado nacional / Biopharmaceutical studies of teophylline-like products at the national market

To perform in vitro release-dissolution studies of sustained release theophylline forms commercialized in Chile, 5 sustained release products were studied according to the specifications of the 7th supplement of the United States Pharmacopoeia Convention. Release and dissolution rates were compared with a rapid release aminophylline form. The identity, validation and active principle content of each product was also studied. All the studied forms complied with the quality requirements of the USP XII. The dissolution rate constants of the products at pH 6 ranged from 0.0583 to 0.2130, compared with 7.1 for the rapid release form. The dissolution of all products, except one, was pH dependent. These results underscore the need to systematically study the quality of pharmaceutical products considered similar, whose differences could have potential risks for patients