ABSTRACT
Hydrophilic drugs could be incorporated into the skin surface by manes of Lipogel. This study aimed to prepare miconazole lipogel with natural ingredients to enhance drug permeability using dimethyl Sulfoxide (DMSO). The miconazole lipogels, A1 (without DMSO) and A2 (with DMSO) were formulated and evaluated for organoleptic evaluation, pH, viscosity, stability studies, freeze-thawing, drug release profile and drug permeation enhancement. Results had stated that prepared lipogel's pH falls within the acceptable range required for topical delivery (4 to 6) while both formulations show good results in organoleptic evaluation. The A2 formulation containing DMSO shows better permeation of miconazole (84.76%) on the artificial skin membrane as compared to A1 lipogel formulation (50.64%). In in-vitro drug release studies, A2 for-mulation showed 87.48% drug release while A1 showed just 60.1% drug release from lipogel. Stability studies were performed on model formulations under environmental conditions and both showed good spreadibility, stable pH, free of grittiness and good consistency in formulation. The results concluded that A2 formulation containing DMSO shows better results as compared to DMSO-free drug lipogel.
Subject(s)
Dimethyl Sulfoxide , Drug Liberation , Gels , Miconazole , Permeability , Miconazole/administration & dosage , Miconazole/chemistry , Miconazole/pharmacokinetics , Dimethyl Sulfoxide/chemistry , Viscosity , Drug Stability , Hydrogen-Ion Concentration , Skin Absorption/drug effects , Chemistry, Pharmaceutical , Drug Compounding , Antifungal Agents/administration & dosage , Antifungal Agents/chemistry , Antifungal Agents/pharmacokinetics , Administration, CutaneousABSTRACT
BACKGROUND: The benefit of apixaban to reduce stroke risk in morbidly obese patients with nonvalvular atrial fibrillation (AF) is still undetermined. The International Society of Thrombosis and Hemostasis recommends avoiding the use of direct oral anticoagulants (DOAC)s in morbidly obese patients (body mass index > 40 or weight > 120 kg) because of limited clinical data. This exploratory study aims to evaluate the effectiveness and safety of using apixaban in morbidly obese (body mass index (BMI) ≥ 40) patients with AF. METHODS: An exploratory retrospective cohort study was conducted at a single-center, including adult patients with non-valvular AF using apixaban between 01/01/2016 and 31/12/2019. Patients were excluded if they were known to have liver cirrhosis Child-Pugh C, mechanical valve, serum creatinine > 1.5 mg/dL, follow up < 3 months, or using apixaban with a dose of ≤5 or > 10 mg/day. Included patients were categorized into two groups based on their BMI (BMI<40 Vs. BMI ≥ 40). The primary outcome was all thrombotic events, while the secondary outcomes were major and minor bleeding after apixaban initiation. Propensity score (PS) matching was used (1:1 ratio) based on the patient's age, gender, and HAS-BLED score. RESULTS: A total of 722 patients were eligible; 254 patients were included after propensity score matching based on the selected criteria. The prevalence of all thrombotic events was similar between the two groups in the first year of apixaban initiation (OR (95%CI): 0.58 (0.13, 2.5), p-value = 0.46). In addition, the odds of developing major and minor bleeding were not statistically significant between the two groups (OR (95%CI): 0.39 (0.07, 2.03), p-value = 0.26 and OR (95%CI): 1.27 (0.56, 2.84), p-value = 0.40), respectively). CONCLUSION: This exploratory study showed similar effectiveness and safety of apixaban use in both morbid and non-morbid obese patients with non-valvular AF. However, a larger randomized controlled trial with a longer follow-up period needs to confirm our findings.
