A Novel Semi-Solid Self-Emulsifying Formulation of Aprepitant for Oral Delivery: An In Vitro Evaluation.

Aprepitant is the first member of a relatively new antiemetic drug class called NK1 receptor antagonists. It is commonly prescribed to prevent chemotherapy-induced nausea and vomiting. Although it is included in many treatment guidelines, its poor solubility causes bioavailability issues. A particle size reduction technique was used in the commercial formulation to overcome low bioavailability. Production with this method consists of many successive steps that cause the cost of the drug to increase. This study aims to develop an alternative, cost-effective formulation to the existing nanocrystal form. We designed a self-emulsifying formulation that can be filled into capsules in a melted state and then solidified at room temperature. Solidification was achieved by using surfactants with a melting temperature above room temperature. Various polymers have also been tested to maintain the supersaturated state of the drug. The optimized formulation consists of CapryolTM 90, Kolliphor® CS20, Transcutol® P, and Soluplus®; it was characterized by DLS, FTIR, DSC, and XRPD techniques. A lipolysis test was conducted to predict the digestion performance of formulations in the gastrointestinal system. Dissolution studies showed an increased dissolution rate of the drug. Finally, the cytotoxicity of the formulation was tested in the Caco-2 cell line. According to the results, a formulation with improved solubility and low toxicity was obtained.

In Vitro Evaluation of a Solid Supersaturated Self Nanoemulsifying Drug Delivery System (Super-SNEDDS) of Aprepitant for Enhanced Solubility.

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.

In-vitro evaluation of dendrimeric formulation of oxaliplatin.

The aim of this study is, preparing various dendrimeric formulations of oxaliplatin and investigating their properties. First of all, the solubility enhancement capabilities of polyamidoamine (PAMAM) G3.5 and PAMAM G4.5 dendrimers were investigated. The results showed that oxaliplatin solubility mostly increasing linearly with dendrimer concentration. Additionally, the increase was more notable in PAMAM G4.5 dendrimers. Then, drug-dendrimer complexes were prepared in different mediums, since the medium used can affect the amount of drug-loaded to dendrimers. Prepared complexes were examined for loading capacity and loading efficiency. It was found that PAMAM G4.5 dendrimers can complex with 2- to 5-fold more oxaliplatin than PAMAM G3.5. Finally, oxaliplatin was modified to a platinum (IV) compound to prepare chemical drug-dendrimer conjugates. Ester bonds were established by Steglich esterification through the hydroxyl group of modified oxaliplatin and the carboxyl groups of the dendrimers. The formulations were characterized by UV, IR, NMR spectroscopy, and dynamic light scattering techniques. PAMAM G3.5 conjugate was further evaluated for the cytotoxicity test. The IC50 value of PAMAM G3.5 conjugate was found as 0.72 µM. For unmodified oxaliplatin, this value was 14.03 µM. As a result, a dendrimer-based drug delivery system that has been found promising for further improvement has been developed successfully.