Desarrollo de formulaciones galénicas de Azitromicina y Loperamida

Abstract

This work proposes the design, development, manufacturing and evaluation of novel oral disintegrating tablets (ODTs) of loperamide HCl (CBD-LH), with special emphasis on disintegration and dissolution studies. The main goal was augmenting the adherence to symptomatic treatment of acute nonspecific diarrhea in soldiers who are exposed to diverse kinds of hostile environments, in combination with an antibiotic, Azithromycin (AZM). ODTs were prepared by the direct compression method from galenic development to the industrial scale technique, thanks to strategic and support actions between the Spanish Army Force Lab and the Department of Biomedical Sciences. A «Lean manufacturing» management system due to an industrial manufacturing line was also proposed to maintain and improve the industrial manufacturing line. Selected CBD-LH, «proposed formula nº14 and nº15», complied with the guidelines required in the Pharmacopoeia in terms of hardness regarding hardness, weight variation, thickness, friability, drug content, wetting time, percentage of water absorption, disintegration time, and in vitro dissolution profile with the guarantee of stability studies of more than 20 months. ODT «proposed formula nº15», was the most suitable option, as it obtained better results in its physical-chemical characterization. For its part, the compatibility of the drugs with the selected excipients was verified by differential scanning calorimetry (DSC), Fourier transform infrared spectrophotometry (FT-IR) and scanning electron microscopy (SEM) studies, which ensures the quality, safety and efficacy of the drug obtained. Likewise, two methods were developed and validated using high performance liquid chromatography (HPLC), in both cases applied also to civil drugs. The first one for the CBD-LH developed representing a tool for the assurance of its quality and safety in the different stages of its development, and in the intermediate product, including the stability study of the finished product. The second one for military AZM tablets as a tool to control the finished product.