Kwak, Seong Shin Lee, Eun Seok Yoon, Ho Yub Kim, Chang Hyun Goo, Yoon Tae Kang, Myung Joo Lee, Sangkil Lee, Bong Sang Jeon, Hong Ryeol Oh, Chang Hyun Choi, Young Wook 2024-01-19T21:33:29Z 2024-01-19T21:33:29Z 2022-01-25 2018-10 1177-8881 https://pubs.kist.re.kr/handle/201004/120820 Purpose: To develop an immediate release-type tablet containing varenicline salicylate (VRC-S), a smoking cessation agent, formulation and stability studies were performed. The in vitro dissolution and in vivo pharmacokinetic (PK) behavior of the tablets were compared with those of the commercial product (Champix) as a reference. Materials and methods: The characteristics of the powder were investigated by particle morphology, size distribution, solubility, hygroscopicity, differential scanning calorimetry, and powder X-ray diffraction. Based on the drug-excipient compatibility test, different VRC-S tablets were prepared with the selected excipients through direct compression or wet granulation method and subjected to a dissolution test. The stability of the most promising VRC-S tablet (F4) was evaluated under accelerated conditions (40 degrees C and 75% relative humidity). Further, the dissolution and human pharmacokinetic profiles of the F4 tablet and Champix were compared. Results: VRC-S showed a positively skewed unimodal size distribution with a specific surface area of 2.02 m(2)/g, single endothermic peak of 225.2 degrees C in differential scanning calorimetry, crystalline internal structure in powder X-ray diffraction, aqueous solubility of 244.7 mg/mL, and hygroscopicity of 0.256 mg/g. The wet granulation method was preferred for tablet preparation and employed the following excipients: microcrystalline cellulose and anhydrous dibasic calcium phosphate as diluents, croscarmellose sodium as a disintegrant, and colloidal silicon dioxide and magnesium stearate as lubricants. The F4 tablet was stable for 6 months under accelerated conditions. The dissolution of VRC was pH independent, revealing f(2) values of 76.49 and 68.38 at pH 1.2 and pH 6.8, respectively. After the oral administration of F4 tablet and Champix to healthy human volunteers, pharmacokinetic parameters, including time to reach the maximum plasma concentration (T-max), maximum plasma concentration (C-max), and area under the curve from 0 to infinity (AUC(inf)), were compared. The values of 90% CI were 0.972-1.035 for C-max and 0.982-1.075 for AUC(inf), which was indicative of the bioequivalence of both products. Conclusion: VRC-S-containing F4 tablet might be a good candidate for smoking cessation treatment. English DOVE MEDICAL PRESS LTD Immediate release tablet formulation of varenicline salicylate and comparative pharmacokinetic study in human volunteers Article 10.2147/DDDT.S178456 1 DRUG DESIGN DEVELOPMENT AND THERAPY, v.12, pp.3377 - 3392 DRUG DESIGN DEVELOPMENT AND THERAPY 12 3377 3392 N scie scopus 000446694700003 2-s2.0-85055155760 Chemistry, Medicinal Pharmacology & Pharmacy Pharmacology & Pharmacy Article RECEPTOR PARTIAL AGONIST ACTIVE PHARMACEUTICAL INGREDIENTS DRUG-DELIVERY SYSTEM SMOKING-CESSATION BIOAVAILABILITY SPECTROSCOPY VALSARTAN TARTRATE SMOKERS SAFETY varenicline salicylate smoking cessation formulation stability dissolution bioavailability