The association of non-alcoholic fatty pancreas disease and glycemic status

Background:Non-alcoholic fatty pancreas disease (NAFPD) is an emerging clinical entity. NAFPD is characterised by excessive fat deposition in the pancreas in the absence of alcohol consumption. Recent studies suggest that NAFPD might be associated with beta cell dysfunction, insulin resistance and inflammation which might lead to development of diabetes. NAFPD might be used as an initial indicator of glucometabolic disturbances and identify the patients with prediabetes. Methods:This was a cross sectional study in which the glycemic status of 50 patients with NAFPD with ultrasonographic evidence of increased echogenicity of pancreas was assessed and association between glycemic variability and NAFPD was determined. The patients were also assessed for the ultrasonographic evidence of fatty liver.Results:Pre-diabetes was noted in 32% subjects while diabetes was noted in 20% subjects. Thus, 52% patients with NAFPD had abnormal glycemic status. The 48% subjects i.e., 24 patients had normoglycemia. The presence of fattyliver was statistically significant in normoglycemia and diabetes mellitus with p=0.001 and 0.045 respectively. No statistically significant association was noted between fatty liver and prediabetes with p=0.175. No causal relationship was seen between fatty liver and glycemic variability in patients with NAFPD.Conclusions:NAFPD is associated with impaired glycemic status. It is also seen frequently with fatty liver. Its early detection may help to identify the patients with prediabetes who may benefit from timely introduction of interventions to reduce the rising morbidity and mortality due to diabetes mellitus.

Design and optimization of novel in situ gel of mercaptopurine for sustained drug delivery

Mercaptopurine is a purine antagonist, belonging to the class of antimetabolites. Its oral absorption is erratic and variable throughout GIT, with bioavailability of 5-37% and belongs to Biopharmaceutical Classification System (BCS) class IV. The focus of the present study was to improve solubility of mercaptopurine and to release the drug uniformly throughout the GIT by formulating into a novel in situ gel tablet. By in vitro swelling studies, xanthan gum was selected as the best gelling polymer and the tablets were prepared by direct compression. Sodium chloride was used as a release modifier to improve the release of drug from the tablet. A 32 full factorial design was applied to optimize the percentage of xanthan gum and sodium chloride to get desired swelling index and release profile. Tablets were evaluated for weight variation, hardness, friability, disintegration time, drug content, in vitro swelling studies and in vitro dissolution studies. The best optimized formulation showed good swelling index and extended the release up to 12 h, where as conventional tablet released the drug within 45 min. The results indicate that mercaptopurine loaded in situ gel tablet could be effective in sustaining drug release for a prolonged period of time throughout the GIT, which can possibly improve the oral bioavailability.

Mercaptopurine é um antagonista da purina, pertencente à a classe dos antimetabólitos. A sua absorção oral é errática e variável através do TGI, com biodisponibilidade de 5-37 % e pertence à classe IV, de acordo com o Sistema de Classificação Biofarmacêutica. O foco do presente estudo foi melhorar a solubilidade da mercaptopurina e liberar o fármaco uniformemente através do TGI, por meio da nova formulação de comprimidos que se tornam gel in situ. Por meio de estudos de inchamento, a goma xantana foi selecionada como o o melhor polímero gelificante e os comprimidos foram preparados por compressão direta. O cloreto de sódio também foi usado como agente modificador de liberação para aprimorar a liberação do fármaco do comprimido. Aplicou-se planejamento fatorial 32 para otimizar a porcentagem de goma xantana e de cloreto de sódio para se alcançar o índice de inchamento e o perfil de liberação desejáveis. Os comprimidos foram avaliados quanto à variação de peso, dureza, friabilidade, tempo de desintegração, conteúdo de fármaco, estudos in vitro de inchamento e de dissolução. A formulação mais bem otimizada mostrou bom índice de inchamento e liberação prolongada acima de 12 h, em comparação com um comprimido convencional, que libera o fármaco em 45 minutos. Os resultados indicam que a 6-mercaptopurina carregada no comprimido de gelificação in situ poderia ser eficaz para a liberação controlada por período de tempo prolongado através do TGI, o que pode, possivelmente, aprimorar a biodisponibilidade oral.

Solid Dispersion: Methods and Polymers to increase the solubility of poorly soluble drugs.

The solubility behaviour of drugs remains one of the most exigent aspects in formulation development. These days, the number of new chemical entities has dramatically increased having hiccups of poor solubility and poor permeability. Solid dispersion as a dosage form has been established a superior option for the drugs having poor aqueous solubility. Solid dispersions in water-soluble carriers have engrossed considerable interest as a means of improving the dissolution rate and bioavailability of hydrophobic drugs. Although solid dispersions have tremendous potential for improving drug solubility and only a few marketed products using this approach. There are various methods available to improve the solubility of the new drug in which solid dispersion emerged promising. A Solid dispersion generally composed of two components- the drug and the polymer matrix. Numerous methods are existing to prepare the solid dispersions such as melting method, solvent evaporation method, fusion method, kneading method, melting method, spray drying method, co-grinding method, lyophilization technique, hot melt extrusion, melt agglomeration, supercritical fluid (SCF) technology etc. A variety of hydrophilic carriers have been investigated for enhancement of dissolution characteristics and bioavailability of poorly aqueous-soluble drugs. In this review an endeavour is made to discuss about the comprehensive methods of preparation and numerous carriers are used for solid dispersions.