Formulation Development and Evaluation of Loperamide Solid Dispersions

Abstract

Background Loperamide is classified as an essential drug in both the 2019 World Health Organization and Kenya essential medicines lists. It is an opioid mu receptor agonist used in the control and relief of acute non-specific diarrhea, traveler’s diarrhea and chronic diarrhea. Unfortunately, its clinical use is hampered by its poor water solubility that affects its dissolution, negatively impacting its oral bioavailability. The objective of this study is to enhance the solubility and consequently dissolution of Loperamide hydrochloride through the use of hydrophilic polymer blends to prepare solid dispersions through a melt mixing technique. Methods A laboratory comparative design was employed in the study. With quality by design principles used in preformulation studies, with critical material attributes taken into account to design the experimental studies. Drug excipient interactions and miscibility studies using mathematical models were applied to guide excipient selection. Binary solid dispersions of loperamide in polyethylene glycol (PEG) and polyvinyl pyrrolidone (PVP) were prepared through fusion/melt method. With ternary solid dispersions incorporating the surfactant sodium lauryl sulphate into the formulations with highest polymer concentration (1:5). The crystallinity of the prepared solid dispersions was ascertained through Fourier Transform infrared spectroscopy. Dissolution studies were undertaken to illustrate the effect of hydrophilic polymers and the surfactant sodium lauryl sulfate (SLS) on the solubility of loperamide hydrochloride. Results The dissolution profiles of loperamide from the formulated solid dispersions were best described by the Weibull model showing parabolic release. The PEG formulation B1 (1:1) followed by formulation B3 (1:5) depicted the best dissolution profiles. The PEG based formulations had better dissolution and crystallinity characteristics over the ternary and PVP formulations. Quality by design principles proved vital in formulation of the solid dispersions providing a guide for formulation development and process design. Conclusion Preparation of loperamide solid dispersions via the melt method is a feasible dissolution enhancement technique and can be employed in the manufacture of solid dispersions through a continuous hot melt extrusion process.