Tacrolimus (TAC), a non-steroidal anti-inflammatory and immunosuppressive agent, is used for the treatment of atopic dermatitis (AD) and skin immune diseases. TAC-loaded topical hydrogel formulations composed of carbomer, carnosine, transcutol P (diethylene glycol monoethyl ether) and humectant were prepared. For comparison, TAC-loaded topical cream-type formulations were also prepared and commercially available TAC ointment was used as a reference. A drug release study in vitro revealed that the total amount of TAC released from hydrogels over 24 h was approximately 30 times greater than that for the reference formulation. Compared to the reference ointment and creams, carbomer gel formulations showed higher skin permeation and retention of TAC (significantly different at p < 0.05), especially those with more than 10% of transcutol P. Therefore, carbomer gel formulations with sufficient levels of transcutol P are good candidates for skin delivery of TAC and have potential as therapeutic agents for the treatment of AD or immune skin disorders.
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.
CDFR0209, a combination of an immediate-release formulation of omeprazole 40 mg and sodium bicarbonate 1100 mg, has been developed to treat acid-related disorders. We compared the acid inhibitory effects of CDFR0209 and delayedrelease omeprazole (omeprazole-DR, Losec 40 mg) after repeated dosing in Helicobacter pylori-negative healthy adult male subjects. In this 2-period crossover study, 30 subjects were randomized to CDFR0209 or omeprazole-DR daily for 7 days. An ambulatory continuous 24-hour intragastric pH recording was performed at baseline and on days 1 and 7 of each administration period. Integrated gastric acidity was calculated from time-weighted average hydrogen ion concentrations at each hour of the 24-hour record. An analysis of variance model was used to test the pharmacodynamic equivalence of CDFR0209 and omeprazole-DR, using the natural logarithmic transformation of the percent decrease from baseline in integrated gastric acidity for the 24-hour interval after the seventh dose of each omeprazole formulation. The geometric least-squares mean ratios (CDFR0209/omeprazole-DR) of the percent decrease from baseline in integrated gastric acidity was 0.98 (90%CI, 0.93-1.07). Both CDFR0209 and omeprazole-DR are equally effective in decreasing integrated gastric acidity at steady state.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.