Immediate release tablet formulation of varenicline salicylate and comparative pharmacokinetic study in human volunteers

Abstract

PurposeTo 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 methodsThe 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°C and 75% relative humidity). Further, the dissolution and human pharmacokinetic profiles of the F4 tablet and Champix were compared.ResultsVRC-S showed a positively skewed unimodal size distribution with a specific surface area of 2.02 m2/g, single endothermic peak of 225.2°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 f2 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 (Tmax), maximum plasma concentration (Cmax), and area under the curve from 0 to infinity (AUCinf), were compared. The values of 90% CI were 0.972–1.035 for Cmax and 0.982–1.075 for AUCinf, which was indicative of the bioequivalence of both products.ConclusionVRC-S–containing F4 tablet might be a good candidate for smoking cessation treatment.

Development of Pelubiprofen Tromethamine with Improved Gastrointestinal Safety and Absorption

“…Salt formation provides a means of changing the physicochemical and resulting biological properties of a drug molecule without changing the structure of the pharmacologically active moiety. However, the selection of an appropriate salt form that has desirable properties, such as solubility, stability, permeability, and bioavailability, plays an important role in the design and development of the drug [ 14 ]. PEL is a relatively weak acid drug with a pKa of 5.0–5.3 that is practically insoluble in water and has low solubility in acidic media.…”

"Development And Assessment of Immediate Release Nitrofurantoin Tablet and Sustained Release Trimethoprim Tablet: Formulation, Characterization and Comparative Evaluation"

“…Additionally, the bulk and tapped densities were meticulously determined utilizing specialized equipment for tapped density measurement. [9][10] The scanning procedure encompassed a spectral range of 4000 to 400 inverse centimeters and was iterated 20 times at a rate of 2 millimeters per second, maintaining a resolution of 4 centimeters per inverse centimeter. The obtained scan data were thoroughly scrutinized to ascertain the primary drug peaks, identify any positional shifts or distortions in these peaks, and observe the emergence of any additional peaks resulting from interactions with the employed polymers [11][12].…”