RESUMO
Cobalamin (vitamin B12), an essential vitamin with low oral bioavailability, plays a vital role in cellular functions. This research aimed to enhance the absorption of vitamin B12 using sublingual mucoadhesive tablets by increasing the residence time of the drug at the administration site. This research involved the preparation of different 50 mg placebo formulas using different methods. Formulas with disintegration times less than one minute and appropriate physical characteristics were incorporated into 1 mg of cyanocobalamin (S1-S20) using the direct compression method. The tablets obtained were evaluated ex vivo for residence time, and only those remaining for >15 min were included. The final formulas (S5, S8, S11, and S20) were evaluated in several ways, including pre- and post-compression, drug content, mucoadhesive strength, dissolution, and Permeapad® permeation test employed in the Franz diffusion cell. After conducting the evaluation, formula S11 (Eudragit L100-55) emerged as the most favorable formulation. It exhibited a mucoadhesive residence time of 118.2 ± 2.89 min, required a detachment force of 26 ± 1 g, maintained a drug content of 99.124 ± 0.001699%, and achieved a 76.85% drug release over 22 h, fitting well with the Peppas-Sahlin kinetic model (R2: 0.9949). This suggests that the drug release process encompasses the Fickian and non-Fickian kinetic mechanisms. Furthermore, Eudragit L100-55 demonstrated the highest permeability, boasting a flux value of 6.387 ± 1.860 µg/h/cm2; over 6 h. These findings indicate that including this polymer in the formulation leads to an improved residence time, which positively impacts bioavailability.
RESUMO
BACKGROUND: Drug design and development to overcome antimicrobial resistance continues to be an area of research due to the evolution of microbial resistance mechanisms and the necessity for new treatments. Natural products have been used since the dawn of medicine to heal skin infections. The antimicrobial properties of fusidic acid, zinc sulfate, and copper sulfate have been studied and are well known. Furthermore, these compounds have different mechanisms of action in targeting microorganisms, either by inhibiting protein synthesis or bacterial cell walls. Therefore, their combination is expected to have synergistic activity in killing bacteria. However, the synergistic antimicrobial activity has not been evaluated in a cream formulation. Therefore, the objectives of this in vitro study were to develop and evaluate the synergistic efficacy of fusidic acid in combinations with natural products, including oleuropein, thyme oil, zinc sulfate, and copper sulfate, as a cream to eradicate fusidic-acid-resistant microorganisms in skin infections. METHODS: Three different cream formulations were developed, compared, and labeled F1, F2, and F3. The compounds were studied for their antibacterial activity. In addition, the stability of the cream was investigated at 25 °C and 40 °C in plastic jars over three months. RESULTS: The F2 formula has adequate physicochemical properties. Furthermore, it displays stable and better results than the marketed trade product and has potential inhibition zones (ZOI). Interestingly, considerable numbers (9.5%) of fusidic-acid-resistant Staphylococcus aureus (FRSA) isolates possessed a high resistance pattern with MIC ≥ 128 µg/mL. In contrast, most tested FRSA isolates (90.5%) had a low resistance pattern with MIC ≤ 8 µg/mL. CONCLUSION: In conclusion, the F2 cream made with fusidic acid, oleuropein, thyme oil, zinc sulfate, and copper sulfate in the right amounts has stable physical and chemical properties and has potential against FRSA as an antimicrobial agent.
RESUMO
Vitamin D3 is available in oral and injectable dosage forms. Interest in the transdermal route as an alternative to the oral and parenteral routes has grown recently. In this study, several film-forming solutions for the transdermal delivery of vitamin D3 were prepared. They contained 6000 IU/mL of vitamin D3 that formed a dry and acceptable film in less than 5 min after application. The formulations consisted of ethanol and acetone 80:20, and one or more of the following ingredients: Eudragit L100-55, PVP, PG, limonene, oleic acid, camphor, and menthol. Vitamin D3 release was studied from both the film-forming solution and pre-dried films using a Franz diffusion cell. The film-forming solution released a significant amount of vitamin D3 compared to the dry film, which is attributed mostly to the saturation driving force due to the evaporation of volatile solvents. In vitro permeation studies through artificial skin Strat M® membrane revealed that the cumulative amount of vitamin D3 permeated after 24 h under the experimental conditions was around 800 IU across 3.14 cm2. The cumulative permeation curve showed faster permeation in earlier stages. Young's modulus, viscosity, and pH of the formulations were determined. Most of the formulations were stable for 3 weeks.
RESUMO
Alogliptin benzoate, a member of dipeptidyl peptidase-4 inhibitors, is a recent drug developed by Takeda Pharmaceutical Company for the treatment of Type 2 diabetes; it potentiates the effect of incretin hormones through the inhibition of their degradation. Alogliptin can be used alone or in combination therapy. A new sensitive and rapid HPLC method was developed for the determination of alogliptin benzoate in bulk and pharmaceutical dosage forms; it was validated according to ICH and FDA guidelines. The HPLC analysis was performed on the Agilent 1200 system equipped with a Hypersil Gold Thermo Scientific C18 (250 cm × 4.6 mm) 5 µm column, with a mixture of acetonitrile and ammonium carbonate buffer in the ratio of 55 : 45 v/v as the mobile phase, at the flow rate of 1.0 mL/min. The detection was performed at the wavelength (λ) of 277, and the retention time of alogliptin benzoate was around 4 min. The total run time was 6.0 min. The calibration plot gave linear relationship over the concentration range of 85-306 µg/ml. The LOD and LOQ were 0.03 and 0.09 µg, respectively. The accuracy of the proposed method was determined by recovery studies and was found to be 100.3%. The repeatability testing for both standard and sample solutions showed that the method is precise within the acceptable limits. RSD% of the determination of precision was <2%. The results of robustness and solutions stability studies were within the acceptable limits as well. The proposed method showed excellent linearity, accuracy, precision, specificity, robustness, LOD, LOQ, and system suitability results within the acceptance criteria. In addition, the main features of the developed method are low run time and retention time around 4 min.
