Aliaa Nabil ElMeshad

Comparative Study on the Effects of Some Polyoxyethylene Alkyl Ether and Sorbitan Fatty Acid Ester Surfactants on the Performance of Transdermal Carvedilol Proniosomal Gel Using Experimental Design

The aim of this work was to investigate the effects of formulation variables on development of carvedilol (CAR) proniosomal gel formulations as potential transdermal delivery systems. Different non-ionic surfactants; polyoxyethylene alkyl ethers, namely Brij 78, Brij 92, and Brij 72; and sorbitan fatty acid esters (Span 60) were evaluated for their applicability in preparation of CAR proniosomal gels. A 23 full factorial design was employed to evaluate individual and combined effects of formulation variables, namely cholesterol content, weight of proniosomes, and amount of CAR added on performance of proniosomes. Prepared proniosomes were evaluated regarding entrapment efficiency (EE%), vesicle size, and microscopic examination. Also, CAR release through cellulose membrane and permeation through hairless mice skin were investigated. Proniosomes prepared with Brij 72 and Span 60 showed better niosome forming ability and higher EE% than those prepared with Brij 78 and Brij 92. Higher EE% was obtained by increasing both weight of proniosomes and amount of CAR added, and decreasing cholesterol content. Release rate through cellulose membrane was inversely affected by weight of proniosomes. In Span 60 proniosomes, on increasing percent of cholesterol, a decrease in release rate was observed. While in Brij 72 proniosomes, an enhancement in release rate was observed on increasing amount of CAR added. Permeation experiments showed that skin permeation was mainly affected by weight of proniosomes and that Span 60 proniosomal gels showed higher permeation enhancing effect than Brij 72. Proniosomal gel could constitute a promising approach for transdermal delivery of CAR.

Characterization and Optimization of Orodispersible Mosapride Film Formulations

Orodispersible film (ODF) technology offers new possibilities for drug delivery by providing the advantages of oral delivery coupled with the enhanced onset of action and convenience to special patient categories such as pediatrics and geriatrics. In this study, mosapride (MOS) was formulated in an ODF preparation that can be used for treatment of patients who suffer from gastrointestinal disorders, especially difficulty in swallowing due to gastroesophageal reflux disease. Poloxamer 188 was used to solubilize MOS to allow its incorporation into the film matrix. The films were prepared by solvent-casting method using different polymer ratios of maltodextrin and hydroxypropyl methylcellulose and plasticizer levels of glycerol and propylene glycol. A D-optimal design was utilized to study the effect of polymer ratio, plasticizer type, and level on film mechanical properties, disintegration time, and dissolution rate. Statistical analysis of the experimental design showed that the increase of maltodextrin fraction and plasticizer level conferred optimum attributes to the prepared films in terms of film elasticity, film disintegration time, and MOS release rate. The ODF formulations were further tested for moisture sorption capacity, with formulations containing a higher ratio of maltodextrin and percent plasticizer showing more moisture uptake. The optimum film composition was also tested in vivo for film palatability and disintegration time. An optimized mosapride orodispersible film formulation was achieved that could be of benefit to patients suffering from gastrointestinal disorders.

Potential therapeutic effect of nanobased formulation of rivastigmine on rat model of Alzheimer’s disease

Background To sustain the effect of rivastigmine, a hydrophilic cholinesterase inhibitor, nanobased formulations were prepared. The efficacy of the prepared rivastigmine liposomes (RLs) in comparison to rivastigmine solution (RS) was assessed in an aluminium chloride (AlCl3)-induced Alzheimer’s model. Methods Liposomes were prepared by lipid hydration (F1) and heating (F2) methods. Rats were treated with either RS or RLs (1 mg/kg/day) concomitantly with AlCl3 (50 mg/kg/day). Results The study showed that the F1 method produced smaller liposomes (67.51 ± 14.2 nm) than F2 (528.7 ± 15.5 nm), but both entrapped the same amount of the drug (92.1% ± 1.4%). After 6 hours, 74.2% ± 1.5% and 60.8% ± 2.3% of rivastigmine were released from F1 and F2, respectively. Both RLs and RS improved the deterioration of spatial memory induced by AlCl3, with RLs having a superior effect. Further biochemical measurements proved that RS and RLs were able to lower plasma C-reactive protein, homocysteine and asymmetric dimethy-larginine levels. RS significantly attenuated acetylcholinesterase (AChE) activity, whereas Na+/K+-adenosine triphosphatase (ATPase) activity was enhanced compared to the AlCl3-treated animals; however, RLs succeeded in normalization of AChE and Na+/K+ ATPase activities. Gene-expression profile showed that cotreatment with RS to AlCl3-treated rats succeeded in exerting significant decreases in BACE1, AChE, and IL1B gene expression. Normalization of the expression of the aforementioned genes was achieved by coadministration of RLs to AlCl3-treated rats. The profound therapeutic effect of RLs over RS was evidenced by nearly preventing amyloid plaque formation, as shown in the histopathological examination of rat brain. Conclusion RLs could be a potential drug-delivery system for ameliorating Alzheimer’s disease.

Enhanced bioavailability of buspirone hydrochloride via cup and core buccal tablets: formulation and in vitro/in vivo evaluation.

This work aims to prepare sustained release buccal mucoadhesive tablets of buspirone hydrochloride (BH) to improve its systemic bioavailability. The tablets were prepared according to 5×3 factorial design where polymer type was set at five levels (carbopol, hydroxypropyl methylcellulose, sodium alginate, sodium carboxymethyl cellulose and guar gum), and polymer to drug ratio at three levels (1:1, 2:1 and 3:1). Mucoadhesion force, ex vivo mucoadhesion time, percent BH released after 8 h (Q8h) and time for release of 50% BH (T(₅₀%)) were chosen as dependent variables. Additional BH cup and core buccal tablets were prepared to optimize BH release profile and make it uni-directional along with the tablets mucoadhesion. Tablets were evaluated in terms of content uniformity, weight variation, thickness, diameter, hardness, friability, swelling index, surface pH, mucoadhesion strength and time and in vitro release. Cup and core formula (CA10) was able to adhere to the buccal mucosa for 8h, showed the highest Q8h (97.91%) and exhibited a zero order drug release profile. Pharmacokinetic study of formula CA10 in human volunteers revealed a 5.6 fold increase in BH bioavailability compared to the oral commercial Buspar® tablets. Conducting level A in vitro/in vivo correlation showed good correlation (r²=0.9805) between fractions dissolved in vitro and fractions absorbed in vivo.

Lyophilized Sustained Release Mucoadhesive Chitosan Sponges for Buccal Buspirone Hydrochloride Delivery: Formulation and In Vitro Evaluation

This work aims to prepare sustained release buccal mucoadhesive lyophilized chitosan sponges of buspirone hydrochloride (BH) to improve its systemic bioavailability. Chitosan sponges were prepared using simple casting/freeze-drying technique according to 32 factorial design where chitosan grade was set at three levels (low, medium, and high molecular weight), and concentration of chitosan solution at three levels (0.5, 1, and 2%). Mucoadhesion force, ex vivo mucoadhesion time, percent BH released after 8 h (Q8h), and time for release of 50% BH (T50%) were chosen as dependent variables. Additional BH cup and core buccal chitosan sponge were prepared to achieve uni-directional BH release toward the buccal mucosa. Sponges were evaluated in terms of drug content, surface pH, scanning electron microscopy, swelling index, mucoadhesion strength, ex vivo mucoadhesion time, and in vitro drug release. Cup and core sponge (HCH 0.5E) were able to adhere to the buccal mucosa for 8 h. It showed Q8h of 68.89% and exhibited a uni-directional drug release profile following Higuchi diffusion model.

Enhanced corneal permeation and antimycotic activity of itraconazole against Candida albicans via a novel nanosystem vesicle.

Abstract The objective of this study was to investigate the potential of spanlastics as an ophthalmic delivery system to improve the corneal permeability and antimycotic activity of itraconazole (ITZ). Spanlastics containing edge activators, including Tween 20 or 80, were produced by modified ethanol injection method and exhibited a particle size of approximately 287 nm and an entrapment efficiency of more than 88%. Less than 13% ITZ was released from spanlastics over 6 h compared to 35% from conventional niosomes. Spanlastics exerted a 1.34-fold increase in the amount of ITZ permeated through excised bovine cornea after 24 h compared to conventional niosomes. Antimycotic study revealed a significant (p < 0.05) increase in the zone of inhibition of Candida albicans culture demonstrated by spanlastics compared to ITZ powder at the same concentration level (10 mg). In vivo Draize test showed no signs of acute ocular toxicity upon application of the selected spanlastic formulation to the rabbit eye. Results revealed that spanlastics loaded with itraconazole could be a potential nanosystem in ocular drug delivery systems.

Floating furosemide gel beads: in vitro and in vivo evaluation

Buoyant beads enclosing furosemide were prepared by cross-linking chitosan with dioctyl sodium sulphosuccinate (DOSS) and characterized according to: entrapment efficiency, in vitro release, in vitro and in vivo buoyancy. The effect of various factors (DOSS and chitosan concentrations, drug: polymer ratio and loading technique) on bead properties were assessed. Interaction between chitosan and DOSS was evaluated by DSC and FTIR. SEM demonstrated that the dried beads were spherical in shape with an inward cavity enclosing furosemide in the range of 1.8-62.25 %. Most beads floated over SGF for 12 h. Beads retarded the release of furosemide compared to pure drug powder and Lasix tablets. The t 50 % ranged from 1.79-4.1 h and release followed zero or diffusion kinetics. Beads remained buoyant in the stomach of dogs for 6 h. Beads were stable at 40 °C and 75 % RH for 3 months. Results showed that chitosan beads proved to be effective carrier for furosemide, maximizing its therapeutic effect at the site of absorption in a controlled release pattern.

Enhancement of dissolution and oral bioavailability of lacidipine via pluronic P123/F127 mixed polymeric micelles: formulation, optimization using central composite design and in vivo bioavailability study

Abstract This study aims at preparing and optimizing lacidipine (LCDP) polymeric micelles using thin film hydration technique in order to overcome LCDP solubility-limited oral bioavailability. A two-factor three-level central composite face-centered design (CCFD) was employed to optimize the formulation variables to obtain LCDP polymeric micelles of high entrapment efficiency and small and uniform particle size (PS). Formulation variables were: Pluronic to drug ratio (A) and Pluronic P123 percentage (B). LCDP polymeric micelles were assessed for entrapment efficiency (EE%), PS and polydispersity index (PDI). The formula with the highest desirability (0.959) was chosen as the optimized formula. The values of the formulation variables (A and B) in the optimized polymeric micelles formula were 45% and 80%, respectively. Optimum LCDP polymeric micelles had entrapment efficiency of 99.23%, PS of 21.08 nm and PDI of 0.11. Optimum LCDP polymeric micelles formula was physically characterized using transmission electron microscopy. LCDP polymeric micelles showed saturation solubility approximately 450 times that of raw LCDP in addition to significantly enhanced dissolution rate. Bioavailability study of optimum LCDP polymeric micelles formula in rabbits revealed a 6.85-fold increase in LCDP bioavailability compared to LCDP oral suspension.

A pharmaceutical study on chlorzoxazone orodispersible tablets: formulation, in-vitro and in-vivo evaluation

Abstract 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®500, Starlac®, Pearlitol flash®, Prosolv® odt and F-melt® 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®500 showed the shortest wetting time (∼45.33 s), disintegration time (DT) (∼43.33 s) and dissolution (Q15min 100.63%). By increasing the ratio of CLZ: Pharmaburst®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® odt, ODTs failed to disintegrate in an acceptable time >180 s. DT of ODTs using different co-processed excipients can be arranged as follows: Pharmaburst® 500 < F-melt® <Pearlitol flash® <Starlac® <Prosolv® odt. Pharmacokinetic study of the optimum formula F1 (50 mg CLZ) in rabbits using HPLC-UV detector revealed a shorter Tmax (0.333 h) compared with Myofen® 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.

Microemulsion loaded hydrogel as a promising vehicle for dermal delivery of the antifungal sertaconazole: design, optimization and ex vivo evaluation

Abstract The purpose of the present study was to develop and optimize sertaconazole microemulsion-loaded hydrogel (STZ ME G) to enhance the dermal delivery and skin retention of the drug. Following screening of various oils for maximum drug solubility, 12 pseudoternary phase diagrams were constructed using oils (Peceol®, Capryol® 90), surfactants (Tween® 80, Cremophor® EL), a cosurfactant (Transcutol® P) and water. A 21 × 31 × 21 × 31 full factorial design was employed to optimize a ME of desirable characteristics. The MEs were formulated by varying the oil type, oil concentration, surfactant type and surfactant: cosurfactant ratio. Optimized ME formulae F22 [5% Peceol®, 55% Tween® 80: Transcutol® (1:2), 40% water] and F31 [5% Peceol®, 55% Cremophor® EL: Transcutol® (1:2), 40% water] acquired mean droplet size of 75.21 and 8.68 nm, and zeta potential of 34.65 and 24.05 mV, respectively. Since F22 showed higher STZ skin retention during ex vivo studies (686.47 μg/cm2) than F31 (338.11 μg/cm2); hence it was incorporated in 0.5% Carbopol 934 gel to augment STZ skin retention capability. STZ ME G exhibited higher STZ skin retention (1086.1 μg/cm2) than the marketed product “Dermofix® cream” (270.3 μg/cm2). The antimycotic activity against C.albicans revealed increased zones of inhibition for F22 and STZ ME G (35.75 and 30.5 mm, respectively) compared to Dermofix® cream (26 mm). No histopathological changes were observed following topical application of STZ ME G on rats’ skin (n = 9). Overall, the obtained results confirmed that the fabricated formulation could be a promising vehicle for the dermal delivery of STZ.