Introduction and aim: Olmesartan medoxomil (OLM) is an antihypertensive drug with low oral bioavailability due to extensive first-pass metabolism. This study aimed to prepare transetho somes (TEs) for enhancing the transdermal delivery of OLM to avoid its oral problems. Methods: TE formulae were prepared utilizing 5 1 .3 1 full factorial design using various surfactants (SAAs) and different phospholipid-to-SAA ratios. The formulae were characterized regarding their entrapment efficiency percentage (EE%), particle size (PS), polydispersity index (PDI), zeta potential (ZP), and the amount of drug released after 6 hours (Q6h). Design Expert ® software was employed to select the optimum formula. Results: The optimum formula (TE14) had an EE% of 58.50%±1.30%, PS of 222.60±2.50 nm, PDI of 0.11±0.06, ZP of-20.80±0.30 mV, and Q6h of 67.40%±0.20%. In addition, TE14 was compared to transferosomes (TFs) in terms of elasticity and was found to show higher deformability index. Further, evaluation of ex vivo permeation using both rat and shed snake skin showed higher permeability of TE14 compared to TFs and OLM suspension. Confocal laser scanning microscopy confirmed the capability of the fluoro-labeled TE14 to penetrate deep within the skin, while the histopathological study confirmed its safety. TE14 successfully maintained normal blood pressure values of rats up to 24 hours. Moreover, TE14 showed superiority in dermatokinetic study when compared with drug suspension. Conclusion: Taken together, the obtained results confirmed the potential of employing TEs as a successful carrier for the transdermal delivery of OLM.

Introduction The intention of this work was to load olmesartan medoxomil (OLM), a sparsely water soluble antihypertensive bioactive with low oral bioavailability (26%), into PEGylated bilosomes (PBs) for augmenting its transdermal delivery. PBs contain PEGylated single chain edge activator besides the components of traditional bilosomes (Span 60, cholesterol and bile salts). The PEG gives further resilience to vesicle membrane and is speculated to augment both permeability and bioavailability of OLM. Methods A 2 4 factorial experiment was constructed to inspect the impact of diverse variables on vesicles’ features and sort out the optimal formula adopting Design Expert ® software utilizing thin film hydration technique. Vesicles’ evaluation was done by finding out entrapment efficiency percent (EE%), particle size (PS), polydispersity index (PDI), zeta potential (ZP) and amount of drug released after 6 hrs (Q6h). The optimal formula was selected and characterized for further investigations. Results The optimal formula (PB15) showed spherical vesicles with EE% of 72.49±0.38%, PS of 559.30±10.70 nm, PDI of 0.57±0.15, ZP of −38.35±0.65 mV and Q6h of 59.60±0.24%. PB15 showed higher deformability index (28.39±5.71 g) compared to traditional bilosomes (5.88±0.90 g) and transethosomes (14.94±0.63 g). Further, PB15 showed superior skin permeation from rat’s skin relative to the drug suspension. Moreover, confocal laser scanning microscopy examination revealed efficient penetration of the fluoro-labeled PB15 through skin. Histopathological study ensured the safety of PB15. In addition, in-vivo skin deposition studies showed higher OLM deposition in rat’s skin from PB15 compared to transethosomes and OLM suspension. Furthermore, pharmacodynamic and pharmacokinetic studies performed using male Wistar rats and male Albino rabbits, respectively, showed the superiority of PB15 over oral tablets. PB15 was found to have significantly higher AUC 0–48 and AUC 0–∞ relative to the oral tablets. As well, the relative bioavailability of PB15 was found to be 235.04%. Conclusion Overall, the obtained results confirmed the creditable effect of PB15 for transdermal delivery.

Solid lipid nanoparticles (SLNs) are very potential formulations for topical delivery of antifungal drugs. Hence, the purpose of this research was to formulate the well-known antifungal agent Fluconazole (FLZ)-loaded SLNs topical gel to improve its efficiency for treatment of Pityriasis Versicolor (PV). FLZ-SLNs were prepared by modified high shear homogenization and ultrasonication method using different concentration of solid lipid (Compritol 888 ATO, Precirol ATO5) and surfactant (Cremophor RH40, Poloxamer 407). The physicochemical properties and the in vitro release study for all FLZ-SLNs were investigated. Furthermore, the optimized FLZ-SLN formula was incorporated into gel using Carpobol 934. A randomized controlled clinical trial (RCT) of potential batches was carried out on 30 well diagnosed PV patients comparing to market product Candistan® 1% cream. Follow up was done for 4 weeks by clinical and KOH examinations. The results showed that FlZ-SLNs were almost spherical shape having colloidal sizes with no aggregation. The drug entrapment efficiency ranged from 55.49% to 83.04%. The zeta potential values lie between −21 and −33 mV presenting good stability. FLZ showed prolonged in vitro release from SLNs dispersion and its Carbapol gel following Higuchi order equation. Clinical studies registered significant improvement (p < .05) in therapeutic response (1.4-fold; healing%, 4-fold; complete eradication) in terms of clinical cure and mycological cure rate from PV against marketed cream. Findings of the study suggest that the developed FLZ loaded SLNs topical gels have superior significant fast therapeutic index in treatment of PV over commercially available Candistan® cream.

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The purpose of this study is to formulate in situ implants containing doxycycline hydrochloride and/or secnidazole that could be used in the treatment of periodontitis by direct periodontal intrapocket administration. Biodegradable polymers [poly (lactide) (PLA) and poly (lactide-co-glycolide) (PLGA)], each polymer in two concentrations 25%w/w, 35%w/w were used to formulate the in situ implants. The rheological behavior, in vitro drug release and the antimicrobial activity of the prepared implants were evaluated. Increasing the concentration of each polymer increases the viscosity and decreases the percent of the drugs released after 24 h. PLA implants showed a slower drugs release rate than PLGA implants in which the implants composed of 25% PLGA showed the fastest drugs release. The in vitro drug release and antimicrobial activity results were compared with results of Atridox. Results revealed that the pharmaceutical formulation based on 25% PLGA containing secnidazole and doxycycline hydrochloride has promising activity in treating periodontitis in comparison with Atridox.

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Context: Muscle spasm needs prompt relief of symptoms. Chlorzoxazone is a centrally muscle relaxant. Objectives: The aim of this study was to prepare chlorzoxazone orodispersible tablets (ODTs) allowing the drug to directly enter the systemic circulation and bypassing the first-pass metabolism for both enhancing its bioavailability and exerting a rapid relief of muscular spasm. Materials and methods: ODTs were prepared by direct compression method using Pharmaburst Õ 500, Starlac Õ , Pearlitol flash Õ , Prosolv Õ odt and F-melt Õ as co-processed excipients. Three ratios of the drug to the other excipients were used (0.5:1, 1:1 and 2:1). Results and Discussion: All ODTs were within the pharmacopeial limits for weight and content. ODTs containing Pharmaburst Õ 500 showed the shortest wetting time ($45.33 s), disintegration time (DT) ($43.33 s) and dissolution (Q 15min 100.63%). By increasing the ratio of CLZ: Pharmaburst Õ 500 from 0.5:1 to 1:1 and 2:1, the DT increased from 26.43 to 28.0 and 43.33 s, respectively. By using Prosolv Õ odt, ODTs failed to disintegrate in an acceptable time4180 s. DT of ODTs using different co-processed excipients can be arranged as follows: PharmaburstPharmacokinetic study of the optimum formula F1 (50 mg CLZ) in rabbits using HPLC-UV detector revealed a shorter T max (0.333 h) compared with Myofen Õ capsules (250 mg CLZ) (1.083 h) which is considered a promising treatment, especially for the rapid relief of muscle spasm. Conclusion: It could be concluded that orodispersible tablets are a promising carrier for CLZ designed for management of muscle spasm due to the enhanced dissolution and rapid absorption of the drug through the oral mucosa.