Formulation and Evaluation of Floating Bioadhesive Tablet of Candesartan Cilexetil Using 32 Factorial Designs

Objective: The objective of the work is to formulate candesartan cilexetil floating bioadhesive tablets which can considerably improve the bioavailability of medicine underneath the condition of redoubled continuance of drug in abdomen. Methods: Floating bioadhesive tablet was ready by direct compression of chemical compound like HPMCE15 and Carbopol934p together. Result: After analysis of different evaluation parameter and drug release, F4 batch was selected as promising formulation for delivery of candesartan cilexetil floating bioadhesive tablets with 91.22% drug release at 12th h. Conclusion: Among the further batches, the F4 batch was selected as an optimized batch as a result of the pre-compression and post-compression parameters results area unit satisfactory. Keywords: Candesartan cilexetil, Floating bioadhesive tablets, Polymer, Total floating time.

Repurposing Candesartan Cilexetil as Antibacterial Agent for MRSA Infection

Staphylococcus aureus is an important pathogen causing hospital-acquired infections. Methicillin-resistant S. aureus (MRSA), biofilms, and persisters are highly tolerant to traditional antibiotics and make it difficult to treat. Therefore, new antimicrobial agents are urgently needed to treat hard-to-eradicate diseases caused by this bacterium. In this study, candesartan cilexetil (CC), an angiotensin hypertension drug, had strong antimicrobial activity against S. aureus with minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) of 8–16 μg/ml and 16–32 μg/ml. CC exhibited limited cytotoxicity and low potential to induce drug resistance. In addition, it showed a synergistic antibacterial effect when combined with gentamicin and tobramycin. The effective concentrations to inhibit MRSA biofilm formation were 16–64 μg/ml, and intractable persisters were killed at 4–8 × MIC. Through the analysis of its mechanism of action, it was evident that the membrane permeability was disrupted as well as the cell structure was damaged. Furthermore, we demonstrated that CC had antibacterial effects in vivo in MRSA-infected murine skin abscess models. In conclusion, these results imply that CC might be a potential antibacterial agent for the treatment of S. aureus-associated infections.

Formulation and Bioavailability of Novel Mucoadhesive Buccal Films for Candesartan Cilexetil in Rats

Candesartan cilexetil (CC) is an antihypertensive drug. It has low solubility and faces hepatic first-pass metabolism after oral ingestion. We formulated bioadhesive buccal films and studied the respective drug pharmacokinetics. Different bioadhesive films were prepared (40, 80, 120, 160, 200, and 240 mg CC per film) by using the solvent casting method. The drug concentrations used affect the drug entrapment mechanism, which was reflected in the film physicochemical properties like thickness, weight, drug content, bioadhesion, and drug release. Low drug concentration (F2, 40 mg per film) led to minute drug crystal dispersion while increasing the drug concentration (F7, 240 mg per film) showed drug crystal encapsulation, which affects the drug release. The drug pharmacokinetic from the prepared films was studied compared to the oral form by serial blood sampling via an inserted catheter in the carotid of rats. High-Performance Liquid Chromatography assay was used to measure the plasma concentration of CC in different forms. Compared to other films, the F2 showed the highest maximal concentration (Cmax) and the lowest elimination half-life (t1/2). Bioadhesion buccal film of CC has better bioavailability, especially at low concentrations. The ease, robustness, and ruggedness of the preparation suggests the same procedure for drugs like CC.

PREPARATION AND IN VIVO EVALUATION OF CANDESARTAN CILEXETIL SOLID DISPERSIONS

Objective: The present study aims at development of solid dispersions (SD) of candesartan cilexetil for enhanced solubility and bioavailability. Methods: About 18 SD formulations of candesartan cilexetil were prepared by solvent evaporation technique and evaluated. The in vitro release studies were conducted and the best formulation chosen was further characterized for Fourier transform infrared spectroscopy, Scanning electron microscope, X-ray, and stability. The in vivo evaluation study conducted in rats. Results: The formulation SD16 containing drug and Soluplus in 1:3 ratio along with 2% selective laser sintering was chosen optimal based on drug content (99.08%), and drug release (99.7%). In vivo studies conducted on SD16 showed that mean time to peak concentration (Tmax) was 2.0±0.05 and 4±0.2 h for the optimized and pure drug, respectively, while mean maximum drug concentration (Cmax) was 570.63±2.65 ng/mL and was significant as compared to the candesartan pure drug 175.146±0.07 ng/mL. Area under curve AUC0-∞ infinity for candesartan SD16 was higher (4860.61±1.05 ng.h/ml) than pure drug suspension 1480±1.72 ng.h/ml. Conclusion: Hence, the developed SD formulations enhanced the bioavailability of drug by 3 folds.