Gamal A. Shazly

Itraconazole-hydroxypropyl-β-cyclodextrin loaded deformable liposomes: In vitro skin penetration studies and antifungal efficacy using Candida albicans as model

The study aimed to develop novel ITZ-loaded deformable liposomes (DL) in presence of hydroxypropyl-β-cyclodextrin (HPβCD) (DL-CD) to enhance antifungal activity. These formulations have been reported as conceivable vesicles to deliver drug molecules to the skin layers. The efficiency of the prepared systems was compared with conventional liposomes (CL) and ITZ solution. The developed liposomes were characterized for particle size, entrapment efficiency (EE %), deformability, stability, and morphology of the vesicles. In addition, ex vivo penetration and antifungal activity were evaluated. It was found that the presence of HPβCD played a significant role in reducing the vesicle size to nano range. The deformability study and TEM images revealed that membrane deformability of DL and DL-CD was much higher than that of CL. Moreover, DL-CD enhanced the amount of ITZ in SC and deeper skin layers compared to DL and CL. The antifungal activity of ITZ-loaded deformable liposomes remained intact compared to ITZ solution. It can be concluded that deformable liposomes in the presence of HPβCD may be a promising carrier for effective cutaneous delivery of ITZ.

Comparison of Dialysis and Dispersion Methods for In Vitro Release Determination of Drugs from Multilamellar Liposomes

The aim of these studies was to compare dialysis and dispersion methods for determining in vitro release of propranolol, metoprolol, pindolol, and atenolol from multilamellar liposomes. Multilamellar vesicles (MLV) were prepared using hydrogenated soy-lecithin phospholipon 90H (Ph 90H) as the primary lipid. The same volume of pH 7.4 phosphate buffered saline was used as a receptor medium for both methods. Samples were withdrawn, and drug concentration was determined using HPLC. All drug-containing liposomes exhibited an initial burst release followed by a slower rate of release. The rate and extent of drug release from MLV was dependent on the physicochemical properties of the drug. For all drugs investigated, the rate of release was higher for the dispersion method as compared with the dialysis method.

Utilizing Pluronic F‐127 and Gelucire 50/13 Solid Dispersions for Enhanced Skin Delivery of Flufenamic Acid

Strategy, Management and Health Policy Preclinical Research

Predicting the in vivo release from a liposomal formulation by IVIVC and non-invasive positron emission tomography imaging.

This study aimed to predict the in vivo performance from the in vitro release of a low-molecular weight model compound, [(18)F]-2-fluoro-2-deoxy-d-glucose ([(18)F]FDG), from liposomes and by means of positron emission tomography (PET). Liposomes composed of hydrogenated phosphatidylcholine (HPC) were prepared by a freeze-thaw method. Particle size distribution was measured by dynamic light scattering (DLS). In vitro release was examined with a dispersion method detecting the radioactivity of [(18)F]FDG. In vivo release of [(18)F]FDG, following i.p. injection of the liposomes in rats, was determined by using a Micro-PET scanner. Convolution was performed to predict the in vivo profiles from the in vitro data and to establish an in vitro-in vivo correlation (IVIVC). The in vivo predictions slightly underestimated the experimentally determined values. The magnitude of the prediction errors (13% and 19%) displayed a satisfactory IVIV relationship leaving yet room for further improvement. This study demonstrated for the first time the use of PET in attaining an IVIVC for a parenterally administered modified release dosage form. It is therefore possible to predict target tissue concentrations, e.g., in the brain, from in vitro release experiments. IVIVC using non-invasive PET imaging could thus be a valuable tool in drug formulation development, resulting in reduced animal testing.

Biological investigation of a supersaturated self-nanoemulsifying drug delivery system of Piper cubeba essential oil

Piper cubeba essential oil (PCEO) is used in many ailments but its mechanism of action is not very well reported especially in the case of pain and inflammation. Therefore, in this work, the mechanism of its anti-inflammatory activity alone and as a supersaturated self-nanoemulsifying drug delivery system (S-SNEDDS) was evaluated. S-SNEDDS formulations of PCEO were developed by an aqueous phase titration method. Thermodynamically stable S-SNEDDSs were characterized based on their droplet size, polydispersity index, zeta potential, viscosity, refractive index, % transmittance and surface morphology. Based on the best physicochemical parameters, the S-SNEDDS F1 was selected for biological investigations in rats. The dose of pure PCEO was 400 mg kg−1 body weight while the S-SNEDDS F1 was administered in two different doses i.e. 40 mg kg−1 and 80 mg kg−1 body weight. The results of this work indicated that pretreatment of PCEO and the S-SNEDDS F1 reduced the exudate volume and polymorphonuclear cell number significantly. Moreover, the levels of MPO, NO and proinflammatory cytokines (TNF-α and IL-β) were also reduced by PCEO and the S-SNEDDS F1 and this observation was also supported by histological observation. The results of the S-SNEDDS F1 were superior compared to PCEO alone even at significantly lower doses. These results indicate the potential of a developed S-SNEDDS in enhancing the therapeutic efficacy of PCEO.

Measurement and evaluation of the effects of pH gradients on the antimicrobial and antivirulence activities of chitosan nanoparticles in Pseudomonas aeruginosa

Objective The purpose of this study was to study the antimicrobial activity of chitosan nanoparticles (CSNPs) on Pseudomonas aeruginosa with special emphasis on their sensitivity to pH and the effect of pH on their activity. Methodology Antimicrobial activity of CSNPs against Pseudomonas aeruginosa at different pH was tested using broth dilution method. Further assessment of antivirulence activity and sensitization of CSNPs on Pseudomonas aeruginosa were examined. Results Significant antimicrobial effects of CSNPs against Pseudomonas aeruginosa were detected at slightly acidic pH 5, whereas the activity was abolished at a pH of greater than 7. The antivirulence activity of CSNPs was then investigated and treatment with CSNPs (1000 ppm) resulted in a significant reduction or even complete inhibition of pyocyanin production by P. aeruginosa compared with untreated P. aeruginosa indicating the antivirulence activity of CSNPs. CSNPs also sensitized P. aeruginosa to the lytic effects of sodium dodecyl sulfate (SDS); such sensitization was not blocked by washing chitosan-treated cells prior to SDS exposure revealing that CSNPs disturb the outer membrane leading to irreversible sensitivity to detergent even at low concentration (100 ppm). Conclusions These findings highlight CSNPs as potentially useful as indirect antimicrobial agents for a variety of applications.

Formulation and Evaluation of Fluconazole Mucoadhisive Vaginal Tablets

The Mucoadhesive drug delivery system has occupied an important place in the field of pharmaceutical research. Mucoadhesive tablets prolong the residence time of the drug at the site of application and provide extended therapeutic effect. Mucoadhesive tablets have been prepared for various sites thus offering localization as swell as systemic control of drug release. The present study focuses on the concept of formulation of fluconazole as a mucoadhesive vaginal tablet, for improving the sustained release of drug and localized action of the drug. Different polymers, such as Hydoxypropylmethylcellulose M 15, Carbopol71G-NFand Guar Gum were used with different concentrations in order to get the desired sustained release profile over a period of more than12 hrs. The tablets were prepared by direct compression method. All the formulations were evaluated for crushing strength, friability, swelling behavior, adhesion time, drug content and in vitro drug release profile. All the formulation tested showed good physical and adhesive properties. It was found that the controlled release rate of the formulation increases with increasing polymer concentration. Kinetican modeling of release data supports an anomalous non-fickian release Original Research Article Mahours et al.; BJPR, 14(2): 1-10, 2016; Article no.BJPR.30629 2 behavior. The antimycotic activity of selected formulations containing fluconazole (100 mg) was determined using an agar diffusion technique. Formulations tested showed activity against C. albicans.

Propafenone HCl fast dissolving tablets containing subliming agent prepared by direct compression method

Propafenone HCl (PPH), an antiarrhythmic drug, has a bitter taste, short half-life, delayed drug dissolution and side effects. Thus, the purpose of this work is to develop orally fast dissolving tablets (OFDTs) containing PPH to provide a rapid drug dissolution and subsequently give rapid onset of action of PPH as an antiarrhythmic drug. Moreover, OFDTs of PPH reduce its side effects and improve its bioavailability. Propafenone HCl (PPH), an antiarrhythmic drug, has a bitter taste, short half-life, delayed drug dissolution and side effects. Direct compression method was used for the preparation of 15 formulations OFDTs containing PPH using directly compressible excipients, subliming agent and superdisintegrants. The prepared tablets were undergone physical characterization, in vitro dissolution and stability studies. All pre- and post-compression tests met the pharmacopoeia specifications. In vitro dissolution of the prepared PPH OFDTs exhibited high dissolution rate than compared to the marketed tablets. It was found that the tablets prepared by using the higher concentration of crospovidone were found to dissolute the drug at a faster rate when compared to other concentrations. A formula containing croscarmellose sodium showed the higher present of PPH dissolved as compared to the other formulations. It was concluded that PPH OFDTs were formulated successfully with acceptable physical and chemical properties with rapid disintegration in the oral cavity, rapid onset of action, and enhanced patient compliance. It was found that F10 showed good stability upon storage at 25 and 40 °C for 3 months. Formulation of PPH OFDTs can result in a significant improvement in the PPH bioavailability since the first pass metabolism will be avoided.

Formulation and evaluation of docetaxel nanosuspensions: In-vitro evaluation and cytotoxicity

Objective The aim of the present study was to formulate the anticancer drug; docetaxel (DOX) as nanoparticles to enhance its biological activity. Methodology Solvent precipitation method was used to prepare DOX-loaded nanoparticles and was stabilized by different concentrations of hydroxypropyl methylcellulose (HPMC, E5) and sodium deoxycholate (SDC). Results The results showed that the particle size of the prepared DOX nanoparticles stabilized by SDC was small in comparison to those stabilized by the corresponding HPMC concentrations. The smallest particle size (83.97 nm) was obtained by using SDC as stabilizer at 5% level with zeta potential of −13.6 mV. It was concluded that increasing the stabilizer concentration resulted in increase in both initial and overall cumulative drug release. The release rate in case of nanoparticles stabilized by 5% SDC was 33% and 87% after 1 and 24 h respectively. The results showed that a significant reduction in the viability of FRO cells was observed at all tested time intervals in case of nanoparticles stabilized by 5% SDC at concentrations of 100 and 1000 μM/ml. In contrast, no signs of cytotoxicity was observed for nanoparticles stabilized by 5% HPMC at 10 and 100 μM/ml concentrations.

Novel chlorhexidine dermal patches, preparation characterization and antimicrobial evaluation

The purpose of this work is to develop chlorhexidine dermal patches using Eudragit® RL100 as the patch forming polymer. Solvent casting technique was employed in the preparation of the patches. The prepared patches, the corresponding physical mixtures, and the individual ingredients were physicochemically characterized by differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) to investigate drug-excipient interactions. The results of the incompatibility studies indicated that the drug was molecularly distributed in Eudragit RL100 matrix. The developed patches were evaluated in terms of tensile strength, percentage of elongation, patch weight, surface pH, content uniformity, and drug dissolution profile. The developed chlorhexidine-medicated patches were flexible, transparent, homogenous, elegant, and smooth. Evaluation of the antimicrobial activity of the developed patches showed effective antimicrobial action against varieties of microorganisms.