Tackling acne vulgaris by fabrication of tazarotene-loaded essential oil-based microemulsion: In vitro and in vivo evaluation.

This study aimed to formulate and optimize an anti-acne drug namely tazarotene (TZR) in essential oil-based microemulsion (ME) using either Jasmine oil (Jas) or Jojoba oil (Joj). TZR-MEs were prepared using two experimental designs (Simplex Lattice Design®) and characterized for droplet size, polydispersity index, and viscosity. Further in vitro, ex vivo, and in vivo investigations were performed for the selected formulations. Results revealed that TZR-selected MEs exhibited suitable droplet size, homogenous dispersions, and acceptable viscosity, in addition to spherical-shaped particles in morphology. The ex vivo skin deposition study showed a significant TZR accumulation in all skin layers for the Jas-selected ME over the Joj one. Further, TZR didn't show any antimicrobial activity against P. acnes, however, it was boosted when it was incorporated into the selected MEs. The in vivo study results of the infected mice ears induced by P. acnes revealed that our selected MEs successfully reached a high level of ear thickness reduction of 67.1% and 47.4% for Jas and Joj selected MEs, respectively, versus only 4% for the market product. Finally, the findings confirmed the ability to use essential oil-based ME, particularly with Jas, as a promising carrier for topical TZR delivery in the treatment of acne vulgaris.

Evaluation of two different approaches of health education (Tailored leaflet vs Video) on referral compliance for prosthetic replacement of missing teeth among the patients at a university dental care center.

BACKGROUND: Prosthodontic replacement of missing teeth is necessary to maintain function, aesthetics and prevent further oral complications. OBJECTIVE: To assess whether health education 'video' increased prosthodontics treatment demand for replacing missing teeth compared to traditional health education (IEC) 'leaflet' among patients visiting a university dental care centre, Saudi Arabia. METHODS: A non-randomized educational intervention was conducted among the patients who had missing teeth. 350 participants were divided equally into two interventions groups- health education leaflet group and health education video group. Two major variants were ascertained; demand for prosthodontic dental care and awareness (knowledge) about importance of replacement of missing teeth. These two variants were studied for the difference in the scores between base line and at the end of the program i.e. after 3 months. Bivariate analysis was done with Chi square test, Mc Nemar Chi-square test and Wilcoxon matched-pairs tests and finally binary logistic regression analysis was done. RESULTS: Final analysis included 324 participants. There was improvement in both knowledge and demand for prosthodontic care in both the groups after health education, but statistically significant improvement in demand for dental care was observed in the health education video group compared to leaflet group (42.9% vs 63.2%). Logistic regression analysis identified that having missing teeth in anterior region of jaw and being into video group were two significant factors associated with increased demand for care. CONCLUSION: Health education video method was found to be effective method compared to leaflets in improving knowledge and demand for replacing missing teeth.

Ion-Triggered In Situ Gelling Intranasal Spray of Dronedarone Hydrochloride Nanocarriers: In Vitro Optimization and In Vivo Pharmacokinetic Appraisal.

The current study aims to develop niosomal nanocarriers for intranasal delivery of dronedarone hydrochloride to ameliorate its limited bioavailability. Niosomes were prepared by ethanol injection method and optimized using 3² full factorial experimental design. Both Span® type (X1) and Span®: cholesterol ratio (X2) were set as independent variables. Vesicle size (Y1), polydispersity index (Y2), zeta potential (Y3), and entrapment efficiency (Y4) were set as responses. The optimal formula was further incorporated into an ion-sensitive in situ gelling polymer for intranasal delivery. Optimal formula (N7), which is composed of Span® 80: cholesterol (1:1), was of the least vesicle size (121.27 ± 13.31 nm), least polydispersity index (0.43 ± 0.073), highest zeta potential (-22.23 ± 2.84 mV) and highest entrapment efficiency (73.44 ± 2.8%). About 75.86% and 60.29% of dronedarone hydrochloride were released from N7 dispersion and in situ gel, respectively, within 12 h, compared to only 13.3% released from a drug-free suspension. In vivo pharmacokinetic study on male New Zealand rabbits resulted in significantly higher Cmax, AUC0-72, and AUC0-∞ of intranasal niosomal in situ gel compared to oral suspension. Almost twofold amplification of relative bioavailability was obtained after intranasal administration of niosomal in situ gel (195.7%) compared to oral suspension.

Design Space Approach for the Optimization of Green Fluidized Bed Granulation Process in the Granulation of a Poorly Water-Soluble Fenofibrate Using Design of Experiment.

In the pharmaceutical industry, the systematic optimization of process variables using a quality-by-design (QbD) approach is highly precise, economic and ensures product quality. The current research presents the implementation of a design-of-experiment (DoE) driven QbD approach for the optimization of key process variables of the green fluidized bed granulation (GFBG) process. A 32 full-factorial design was performed to explore the effect of water amount (X1; 1-6% w/w) and spray rate (X2; 2-8 g/min) as key process variables on critical quality attributes (CQAs) of granules and tablets. Regression analysis have demonstrated that changing the levels of X1 and X2 significantly affect (p ≤ 0.05) the CQAs of granules and tablets. Particularly, X1 was found to have the pronounced effect on the CQAs. The GFBG process was optimized, and a design space (DS) was built using numerical optimization. It was found that X1 and X2 at high (5.69% w/w) and low (2 g/min) levels, respectively, demonstrated the optimum operating conditions. By optimizing X1 and X2, GFBG could enhance the disintegration and dissolution of tablets containing a poorly water-soluble drug. The prediction error values of dependent responses were less than 5% that confirm validity, robustness and accuracy of the generated DS in optimization of GFBG.

Construction of sublingual trilaminated Eszopiclone fast dissolving film for the treatment of Insomnia: Formulation, characterization and In vivo clinical comparative pharmacokinetic study in healthy human subjects.

BACKGROUND: Disturbed sleep can cause to m health problems such as cognitive impairment, depressed mood, and negative effects on cardiovascular, endocrine, and immune function. This study formulates and optimizes Eszopiclone trilaminate fast dissolving film. METHODS: Prepared Eszopiclone trilaminate fast dissolving film (Eszopiclone TFDF) was characterized by disintegration time, drug release, tensile strength (TS), percentage elongation (EB%), folding endurance, taste masking test, and in vitro dissolution test. The selected formulas were F2 (0.5% xanthan gum, 10% propylene glycol), F4 (3% sodium alginate, 10% propylene glycol) and F6 (1.5% pullulan, 10% propylene glycol) were subjected to in vivo study compared to conventional Lunesta® tablet. RESULTS: The results indicated that disintegration time was in the range of 940 m. Drug release was found to be in the field of 78.51%-99.99%, while TS values and EB% differed from 11.12 to 25.74 (MPa) and 25.38%-36.43%, respectively. The folding endurance went between 200 and 300 times. All formulas exhibited acceptable uniformity content, surface pH, film thickness, and a good taste feeling. CONCLUSION: F4 had the highest Cmax (39.741 ± 6.785-µg/l) and lower Tmax (1.063 hr) among other formulas and conventional tablets. Therefore, FDFs' technology could increase the therapeutic effect of Eszopiclone.

Polymeric versus lipid nanocapsules for miconazole nitrate enhanced topical delivery: in vitro and ex vivo evaluation.

Nanocapsules can be equated to other nanovesicular systems in which a drug is entrapped in a void containing liquid core surrounded by a coat. The objective of the present study was to investigate the potential of polymeric and lipid nanocapsules (LNCs) as innovative carrier systems for miconazole nitrate (MN) topical delivery. Polymeric nanocapsules and LNCs were prepared using emulsification/nanoprecipitation technique where the effect of poly(ε-caprolactone (PCL) and lipid matrix concentrations with respect to MN were assessed. The resulted nanocapsules were examined for their average particle size, zeta potential, %EE, and in vitro drug release. Optimum formulation in both polymeric and lipidic nanocapsules was further subjected to anti-fungal activity and ex vivo permeation tests. Based on the previous results, nanoencapsulation strategy into polymeric and LNCs created formulations of MN with slow biphasic release, high %EE, and improved stability, representing a good approach for the delivery of MN. PNCs were best fitted to Higuchi's diffusion while LNCs followed Baker and Lonsdale model in release kinetics. The encapsulated MN either in PNCs or LNCs showed higher cell viability in WISH amniotic cells in comparison with free MN. PNCs showed less ex vivo permeation. PNCs were accompanied by high stability and more amount drug deposition (32.2 ± 3.52 µg/cm2) than LNCs (12.7 ± 1.52 µg/cm2). The antifungal activity of the PNCs was high 19.07 mm compared to 11.4 mm for LNCs. In conclusion, PNCs may have an advantage over LNCs by offering dual action for both superficial and deep fungal infections.

Formulation and Optimization of Nanospanlastics for Improving the Bioavailability of Green Tea Epigallocatechin Gallate.

The present study aimed to investigate the potential of nanospanlastics for boosting the bioavailability of epigallocatechin gallate (EGCG). EGCG has valuable effects like anti-inflammation, anti-oxidation, and anti-tumorigenesis. Unfortunately, it has a low oral bioavailability due to its limited permeation and poor stability. To overcome these pitfalls, EGCG was fabricated as a nanospanlastic. Nanospanlastics are flexible nanovesicles that are composed of surfactants and edge activators (EAs). EAs improve the deformability of spanlastics by acting as a destabilizing factor of their vesicular membranes. EGCG-loaded spanlastics were prepared by an ethanol injection method, according to 23 factorial design, to explore the impact of different independent variables on entrapment efficiency (EE%), % drug released after 12 h (Q12h), and particle size (PS). In vitro characterization, ex vivo intestinal permeation test, and pharmacokinetic study of the optimized formula were performed. A newly developed RP-HPLC technique was adopted for the estimation of EGCG . The optimized formula (F4) demonstrated more prolonged drug release and a significant improvement in the EE%, permeability, deformability and stability than the corresponding niosomes. The pharmacokinetic study investigated that F4 had a more sustained drug release and a higher bioavailability than the conventional niosomes and free drugs. Nanospanlastics could be a promising approach for improving the bioavailability of EGCG.

Proniosomal Telmisartan Tablets: Formulation, in vitro Evaluation and in vivo Comparative Pharmacokinetic Study in Rabbits.

OBJECTIVE: The purpose of this study was to prepare proniosomal vesicles of Telmisartan (TEL) to be compressed into tablets which will be further evaluated in vitro and in vivo. MATERIALS AND METHODS: An experimental design was adopted using surfactants of different HLB values (span 40-brij 35), different cholesterol ratios (20-50%) and different phospholipid types (egg yolk-soyabean). Different responses were measured followed by tablet manufacturing. The highest EE was shown in F3 (85%) while the lowest value was obtained in F7 (8.4%). Finally, zeta potential results were in the range of -0.67 to -27.6 mv. Compressibility percent revealed that F5 showed an excellent flowability characteristic with a value of 9.74±1.61 while F3 and F6 showed good flowability characteristics. By the end of the release, F6 showed approximately 90% drug release. RESULTS: F6 was selected for the in vivo study; Cmax was increased by 1.5-fold while AUC0-∞ also increased significantly by 3-fold when compared with commercial tablet and finally, tmax was increased by 3-fold indicating sustained release pattern. The relative bioavailability was also increased by 3.2-fold. CONCLUSION: The results of this study suggested that the formulation of compressed tablets containing more stable proniosomal powder extended the release of TEL and increased its bioavailability as well.

Assessment Of Spanlastic Vesicles Of Zolmitriptan For Treating Migraine In Rats.

OBJECTIVE: To develop and evaluate zolmitriptan spanlastics (Zol SLs) as a brain-targeted antimigraine delivery system. Spanlastics (SLs) prepared using span 60: tween 80 (70:30%, respectively) gave the highest percentage of entrapment efficiency (EE%). MATERIALS AND METHODS: A total of 60 adult male Wistar albino rats were divided into six groups (n=10 rats/group). Group 1 (Control) comprised rats serving as a negative control. Group 2 was treated with glyceryl trinitrate (NTG) and served as the positive control. Groups 3 (NTG+Zol com), Group 4 (NTG+Zol sol) and Group 5 (NTG+Zol SLs) received commercial zolmitriptan orally, zolmitriptan solution intranasally and Zol SLs F5 intranasally, respectively, 30 min before NTG. Group 6 (Zol SLs) comprised normal rats that received only Zol SLs intranasally. RESULTS: We found decreased Tmax, increased Cmax, AUC0-6, AUC0-∞ and ameliorated behaviour in rats (head scratching) treated with intranasal SLs compared to oral commercial zolmitriptan. CONCLUSION: Our study substantiates the enhanced efficacy of Zol SLs in brain targeting for migraine treatment.

Assessment of the hepatoprotective effect of developed lipid-polymer hybrid nanoparticles (LPHNPs) encapsulating naturally extracted ß-Sitosterol against CCl4 induced hepatotoxicity in rats.

The hepatoprotective effect of ß-Sitosterol (BSS), a natural phytosterol, after being formulated into a suitable pharmaceutical drug delivery system has not been widely explored. BSS was isolated from Centaurea pumilio L., identified and formulated as lipid-polymer hybrid nanoparticles (LPHNPs) using the poly(D,L-lactide-co-glycolide) polymer and DSPE-PEG-2000 lipid in different ratios. The selected formulation, prepared with a lipid: polymer: drug ratio of 2:2:2, had an entrapment efficiency (EE%) of 94.42 ± 3.8, particle size of 181.5 ± 11.3 nm, poly dispersity index (PDI) of 0.223 ± 0.06, zeta potential of -37.34 ± 3.21 and the highest drug release after 24 h. The hepatoprotective effect of the formulation at two different doses against CCl4 induced hepatotoxicity was evaluated in rats. The results showed that the BSS-LPHNPs (400 mg/kg) have the ability to restore the liver enzymes (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)), liver lipid peroxidation markers (malondialdehyde (MDA) and catalase (CAT)), total bilirubin and albumin to their normal levels without inhibitory effect on the CYP2E1 activity. Also, the formulation could maintain the normal histological structure of liver tissue and decrease the cleaved caspase-3 expression. LPHNPs formulation encapsulating natural BSS is a promising hepatoprotective drug delivery system.

Nanogel loaded with surfactant based nanovesicles for enhanced ocular delivery of acetazolamide.

Objective: Intraocular pressure has always been a great challenge for topical ophthalmic drugs. The study aimed to develop ocular surfactant based nanovesicles (NVs) carried in mucoadhesive nanogel providing efficient topical delivery of acetazolamide (ACZ). Methods: For the sake of optimizing formulation parameters, the effect of the type of edge activator and its ratio to sorbitan monostearate (Span 60) on the mean particle size, entrapment efficiency (%EE), and zeta potential (ZP) of produced NVs was investigated. Results: The selected formulation composed of Span 60:sodium deoxycholate with ratio 80:20 showed an average diameter of 202.90 nm, %EE of 90.2%, and ZP of -38.1 mV with a spherical and smooth surface. The ACZ loaded nanovesicles (ACZ-NVs) were embedded in different concentrations of Chitosan-sodium tripolyphosphate (CS-TPP) nanogels. The nanogel prepared using 1.5% CS showed the most promising viscosity, adhesion time, and rheological behavior (118,246 cP, 290 min, and thixotropic behavior, respectively). The in vitro release of ACZ showed a controlled release profile after incorporation in nanogels. The in vivo irritation test showed minimal irritation for the nanogel formulation compared to ACZ topical suspension. The effect of intraocular pressure lowering was significantly prolonged using ACZ-NV nanogels compared to ACZ oral tablets. Histopathological examination emphasized the healing power of CS on retinal atrophy. Conclusion: The research work indicated a promising potential for successful topical delivery of ACZ.

Non-ionic surfactant based vesicular drug delivery system for topical delivery of caffeine for treatment of cellulite: design, formulation, characterization, histological anti-cellulite activity, and pharmacokinetic evaluation.

Cellulite is a common topographical alteration where skin acquires an orange peel or mattress appearance with alterations in adipose tissue and microcirculation. This work aims to develop and evaluate a topical niosomal gel formulae with good permeation to reach the subcutaneous fat layer. Several caffeine niosomal dispersions were prepared and incorporated into gel formulae using Carbopol 940 polymer, chemical penetration enhancers, and iontophoresis, then the prepared gels were applied onto the skin of rats and anticellulite activity of caffeine from the prepared gels compared to that of the commercial product Cellu Destock® was evaluated by histological study of the skin and measurement of plasma level of caffeine passing through the skin using liquid chromatography (LC/MS-MS). Results of histology revealed reduction of size and thickness of fatty layer of rat skin in the following order: FVII > FXIV > Cellu Destock® > FVII + Iontophoresis > FXIV + Iontophoresis. Pharmacokinetic results of caffeine in plasma revealed that Cmax, Tmax, and AUC0-12h decreased in the following order: FXIV > FVII > Cellu Destock®. These results conclude that incorporation of caffeine niosomal dispersion into gel matrix with penetration enhancers and iontophoresis resulted in improvement in penetration of caffeine through the skin into the underlying fatty layer in treatment of cellulite.

Biodegradable polymeric microcapsules for sustained release of riboflavin.

In the current study, a series of polylactic acid and polylactic-co-glycolic acid were prepared in an easy, simple, safe and economically feasible way with yield% greater than 90%. Studying the effect of a catalyst on polymerization process was performed. Riboflavin (RF) was chosen as a model drug and microencapsulated in different (drug: polymer) ratios to modify its performance via o/w emulsion solvent evaporation technique and characterized in terms of the morphology and entrapment efficiency (E.E.) and evaluated via in vitro RF release studies. It has been found that, the release rate consists a burst release at the first 12h, followed by a gradual release over 3days. The cumulative riboflavin release from these microcapsules formulations at the end of 3days was 70% and 80% for PDLA and PDLAGA respectively. The kinetics of release profiles were zero order. The highest (E.E.) of RF obtained among all formulations was 85%.