Abstract
Aprepitant (APR) belongs to Class II of the Biopharmaceutical Classification System (BCS) because of its low aqueous solubility. The objective of the current work is to develop self-nanoemulsifying drug delivery systems (SNEDDS) of APR to enhance its aqueous solubility. Preformulation studies involving screening of excipients for solubility and emulsification efficiency were carried out. Pseudo ternary phase diagrams were constructed with blends of oil (Imwitor® 988), cosolvent (Transcutol® P), and various surfactants (Kolliphor® RH40, Kolliphor® ELP, Kolliphor® HS15). The prepared SNEDDS were characterized for droplet size and nanoemulsion stability after dilution. Supersaturated SNEDDS (super-SNEDDS) were prepared to increase the quantity of loaded APR into the formulations. HPMC, PVP, PVP/VA, and Soluplus® were used as polymeric precipitation inhibitors (PPI). PPIs were added to the formulations at 5% and 10% by weight. The influence of the PPIs on drug precipitation was investigated. In vitro lipolysis test was carried out to simulate digestion of formulations in the gastrointestinal tract. Optimized super-SNEDDS were formulated into free-flowing granules by adsorption on the porous carriers such as Neusilin® US2. In vitro dissolution studies of solid super-SNEDDS formulation revealed an increased dissolution rate of the drug due to enhanced solubility. Consequently, a formulation to improve the solubility and potentially bioavailability of the drug was developed.
Highlights
Aprepitant (APR) is the first commercially available drug from a new class of neurokinin1 (NK1) receptor antagonists
selfnanoemulsifying drug delivery systems (SNEDDS) formulations of APR were successfully prepared with different approaches
Preliminary studies and pseudo ternary phase diagram analysis suggested that formulation contains 20% Imwitor® 988, 60% Kolliphor®
Summary
Aprepitant (APR) is the first commercially available drug from a new class of neurokinin (NK1) receptor antagonists. It acts by reducing the emetic effects of substance P [1]. Substance P is a neuropeptide consisting of 11 amino acids and is an endogenous ligand for NK1 receptors. It acts as a neurotransmitter and is involved in the development of inflammatory and immune responses in the body [2]. Substance P is the most abundant neurokinin in the central nervous system of mammals and plays a key role in the pathophysiology of many events such as delayed emesis due to chemotherapy [1]. APR is used orally in combination with other agents (like corticosteroids) for the prevention of acute and delayed nausea and vomiting associated with highly and moderately emetogenic chemotherapy and for the prevention of post-operative nausea and vomiting [3]
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