Development and optimization of a sublingual tablet formulation for physostigmine salicylate

Abstract

Physostigmine salicylate, a reversible inhibitor of cholinesterase activity (1) may be an effective drug in the management of Alzheimer's disease (2, 3) and may be also used in the treatment of nerve gas poisoning (2). It is readily absorbed from the gastrointestinal tract (1) and undergoes extensive presystemic metabolism (2), which results in poor bioavailability of its oral dosage forms (2, 3). Short elimination half-life of this drug (3) makes repeated injections at short time intervals necessary and causes poor patient compliance. Therefore preparation of a suitable and more effective dosage form of this drug is needed. This study is aimed to design and optimize a sublingual tablet formulation of physostigmine salicylate, an effective drug in Alzheimer's disease and nerve gas poisoning, by means of the D-optimal experimental design methodology. Polyvinyl pyrrolidone, lactose, starch 1500 and sodium starch glycolate were used in the formulations as independent variables. Tablets were prepared by the direct compression method and evaluated for their physical properties (tablet hardness, disintegration time and friability), which were regarded as responses in a D-optimal design. Due to the significance of the special cubic model for data fitted, compared to other models, it was used to examine the obtained results. Response surface plots were plotted to study the tablet properties and the optimized overlay plot was generated based on the results and targets considered for the responses. After verification of the optimum checkpoint formulations, an optimized formulation was chosen due to its desirable physical properties and closely observed and predicted values. Drug assay, content uniformity of the dosage unit, drug dissolution and accelerated stability studies were done on the optimum formulation as further experiments. All the obtained results complied with the requirements of a sublingual tablet formulation.

Formulation Optimization of Hydrodynamically Balanced Oral Controlled Release Bioadhesive Tablets of Tramadol Hydrochloride

“…Tablets require a certain amount of strength or hardness, and resistance to friability, to withstand the mechanical shocks of handling during their manufacture, shipping and packaging. The hardness of a tablet is closely related to its disintegration time and dissolution, and eventually its drug release rate [30]. Tablet hardness monitoring, therefore, is especially important for drug products which possess real or potential bioavailability problems or those sensitive to altered dissolution release profiles as a function of the compressive force applied.…”

Development of canagliflozin nanocrystals sublingual tablets in the presence of sodium caprate permeability enhancer: formulation optimization, characterization, in-vitro , in silico , and in-vivo study

“…The final tablet weight was 400 mg. Powder combinations were crushed using a single-punch machine (Royal Artist, Bombay, India) along with a 12 mm flat bunch and 4000 kg of force. (Bolourchian et al., 2009 ).…”