Superiority of microemulsion-based hydrogel for non-steroidal anti-inflammatory drug transdermal delivery: a comparative safety and anti-nociceptive efficacy study.

Non-steroidal anti-inflammatory drugs (NSAIDs) represent the foundation of pain management caused by inflammatory disorders. Nevertheless, their oral administration induces several side effects exemplified by gastric ulceration, thus, delivering NSAIDs via skin has become an attractive alternative. Herein, microemulsion-based hydrogel (MBH), proliposomal, and cubosomal gels were fabricated, loaded with diclofenac, and physicochemically characterized. The size, charge, surface morphology, and the state of diclofenac within the reconstituted gels were also addressed. The ex-vivo permeation study using Franz cells was performed via the rat abdominal skin. The formulations were assessed in-vivo on mice skin for their irritation effect and their anti-nociceptive efficacy through tail-flick test. Biosafety study of the optimal gel was also pointed out. The gels and their dispersion forms displayed accepted physicochemical properties. Diclofenac was released in a prolonged manner from the prepared gels. MBH revealed a significantly higher skin permeation and the foremost results regarding in-vivo assessment where no skin irritation or altered histopathological features were observed. MBH further induced a significant anti-nociceptive effect during the tail-flick test with a lower tendency to evoke systemic toxicity. Therefore, limonene-containing microemulsion hydrogel is a promising lipid-based vehicle to treat pain with superior safety and therapeutic efficacy.

Tailored Limonene-Based Nanosized Microemulsion: Formulation, Physicochemical Characterization and In Vivo Skin Irritation Assessment.

Purpose: Microemulsion (ME) achieved progressing consequences on both the research and industry levels due to their distinctive properties. ME based-limonene system is considered as a surrogate to the traditional microemulsion composed of conventional oils. Thus, a novel microemulsion based on D-limonene and Gelucire® 44/12 had been designed and evaluated with assessing the factors affecting its physicochemical characteristics and in vivo skin irritation. Methods: The impact of microemulsion components and ratios on the isotropic region of the pseudo-ternary phase diagram was investigated. The optimal formula was evaluated in terms of percentage transmittance, average globule size, size distribution, zeta potential, microscopical morphology, stability under different storage conditions and its effect on the mice ear skin. Results: The results demonstrated that Labrasol® and Labrafil® M 1944 CS had been selected as surfactant and co-surfactant, respectively, due to their emulsifying abilities. The largest isotropic area in the pseudo-ternary phase diagram was at a weight ratio of 4:1 for Labrasol® and Labrafil® M 1944 CS. The optimized microemulsion with 25% w/w of the lipid phase and 58.3% w/w of the aqueous phase displayed an optical transparency of 96.5±0.88 %, average globule size of 125±0.123 nm, polydispersity index of 0.272±0.009, zeta potential of -18.9± 2.79 mV with rounded globules morphology and high stability. The in vivo skin irritation and the histopathological evaluation of microemulsion elucidated its safety profile when applied on the skin. Conclusion: The formulated microemulsion is a prospective aid for an essential oil to minimize its volatility, enhance its stability, and mask its dermal irritant.

Spray-dried pH-sensitive microparticles: effectual methodology to ameliorate the bioavailability of acid labile pravastatin.

Pravastatin is a promising drug utilized in the treatment of hyperlipidemia, yet, its main clinical limitation is due to gastric liability which fractions its oral bioavailability to less than 18%. The purpose of the current study is to encapsulate pravastatin into Eudragit®-based spray-dried microparticles aspiring to overcome its acid liability. With the aim to optimize the microparticles, formulation and process parameters were studied through acid resistance challenging test. Physicochemical characterization of the optimized spray-dried pH-sensitive microparticles namely; in-vitro dissolution, surface morphology, compatibility, and solid-state studies were performed. Moreover, in-vivo evaluation of the microparticles and accelerated stability studies were carried out. The results outlined that polymer to drug ratio at 5:1 and pravastatin concentration at 1%w/w in spray-drying feed solution showed 38.55% and 53.97% encapsulation efficiency, respectively. The significance of process parameters specifically; the flow rate and the inlet temperature on microparticles surface integrity were observed, and optimized until encapsulating efficiency reached 72.37%. The scanning electron microscopical examination of the optimized microparticles illustrate uniform smooth surface spheres entrapping the drug in an amorphous state as proved through Differential Scanning Calorimetry (DSC) and Fourier Transfer Infrared (FTIR) studies. The in-vivo evaluation demonstrated a 5-fold enhancement in pravastatin bioavailability compared to the marketed product. The results provided evidence for the significance of spray-dried pH-sensitive microparticles as a promising carrier for pravastatin, decreasing its acid liability, and improving its bioavailability.

Optimization, physicochemical characterization and in vivo assessment of spray dried emulsion: A step toward bioavailability augmentation and gastric toxicity minimization.

The limited solubility of BCS class II drugs diminishes their dissolution and thus reduces their bioavailability. Our aim in this study was to develop and optimize a spray dried emulsion containing indomethacin as a model for Class II drugs, Labrasol®/Transuctol® mixture as the oily phase, and maltodextrin as a solid carrier. The optimization was carried out using a 2(3) full factorial design based on two independent variables, the percentage of carrier and concentration of Poloxamer® 188. The effect of the studied parameters on the spray dried yield, loading efficiency and in vitro release were thoroughly investigated. Furthermore, physicochemical characterization of the optimized formulation was performed. In vivo bioavailability, ulcerogenic capability and histopathological features were assessed. The results obtained pointed out that poloxamer 188 concentration in the formulation was the predominant factor affecting the dissolution release, whereas the drug loading was driven by the carrier concentration added. Moreover, the yield demonstrated a drawback by increasing both independent variables studied. The optimized formulation presented a complete release within two minutes thus suggesting an immediate release pattern as well, the formulation revealed to be uniform spherical particles with an average size of 7.5µm entrapping the drug in its molecular state as demonstrated by the DSC and FTIR studies. The in vivo evaluation, demonstrated a 10-fold enhancement in bioavailability of the optimized formulation, with absence of ulcerogenic side effect compared to the marketed product. The results provided an evidence for the significance of spray dried emulsion as a leading strategy for improving the solubility and enhancing the bioavailability of class II drugs.

Mucoadhesive liposomes as ocular delivery system: physical, microbiological, and in vivo assessment.

BACKGROUND: Mucoadhesive drug delivery is a promising strategy to overcome ocular biopharmaceutical constraints. OBJECTIVE AND METHODS: Ciprofloxacin HCl-loaded reverse phase evaporation liposomes were coated with different concentrations and molecular weights of mucoadhesive biocompatible chitosan polymer to form chitosomes. This colloidal mucoadhesive system was evaluated in vitro and in vivo with respect to deliver the antibiotic to ocular surface. RESULTS AND CONCLUSION: The results obtained pointed out that liposome coating process resulted in entrapment efficiency reduction and higher chitosan concentration, and molecular weight showed a more pronounced effect. No morphological differences between coated and uncoated liposomes were observed. Diffusion was the drug release mechanism from chitosomes. Concerning rheological behavior, pseudoplastic flow was characteristic to the prepared chitosomal dispersions. In addition, chitosan coating improved the ocular permeation of ciprofloxacin HCl. Microbiologically; this formulated system enhanced antimicrobial activity of ciprofloxacin HCl against both Gram-positive and Gram-negative bacteria. Moreover, this mucoadhesive system was able to inhibit the growth of Pseudomonas aeruginosa in rabbits' eyes for 24 hours when compared to the marketed preparation. In vivo bacterial conjunctivitis model elucidated that symptoms were controlled by the prolonged release formulation such as that done by the marketed product.

Ciprofloxacin liposomes as vesicular reservoirs for ocular delivery: formulation, optimization, and in vitro characterization.

Management of extraocular diseases is mainly limited by the inability to provide long-term drug delivery without avoiding the systemic drug exposure and/or affecting the intraocular structures and poor availability of drugs, which may be overcome by prolonging the contact time with the ocular system, for instance with liposomes. Development and optimization of reverse phase evaporation ciprofloxacin (CPF) HCl liposomes for ocular drug delivery was carried out using a 2(5) full factorial design based on five independent variables. The effects of the studied parameters on drug entrapment efficiency (EE), particle size, and percentage of drug released after 1 and 10 h were investigated. The results obtained pointed out that the molar concentration of cholesterol was the predominant factor that increased the EE% of the drug and the particle size responses. The percentage of drug released after 1 h was significantly controlled by the initial CPF concentration while that after 10 h was controlled by molar cholesterol concentration. The designed liposomes had average particle sizes that ranged from 2.5 to 7.23 microm. In addition, liposomes revealed a fast release during the first hour followed by a more gradual drug release during the 24-h period according to Higuchi diffusion model.