Mohamed A. Attia

Dissolution Rates of Carbamazepine and Nitrazepam Utilizing Sugar Solid Dispersion System

AbstractThe dissolution of carbamazepine and nitrazepam from Its solid dispersions using anhydrous lactose, mannitol, galactose, PEG 6000 and coprecipitate using polyvinylpyrrolidone (PVP) 40,000 was investigated. The dissolution process of capsules containing either carbamazepine or nitrazepam as solid dispersion or coprecipitate followed an apparent first order process. The combination of carbamazepine with sugars (mannitol, lactose, and galactose) caused, in every case, an increase in the dissolution rate of the drug. Carbamazepine-PVP coprecipitate gave the higher dissolution rate than that of the solid dispersions with sugars and PEG 6000. Nitrazepam-lactose system gave higher dissolution rate than the other dispersions and coprecipitate. This enhancement in dissolution rate was much more obvious for the solid dispersions and coprecipitate than for the physical mixtures.

Effect of Particle Size on the Dissolution Rate of Monophenylbutazone Solid Dispersion in Presence of Certain Additives

AbstractMonophenylbutazone is a very sparingly soluble drug. The effect of particle size on the dissolution characteristics of monophenylbutazone in a dissolution medium of 0.1 N hydrochloric acid and 0.1 N hydrochloric acid to which was added 0.005% Tween 80, was carried out. The enhancement of the dissolution rate of the medicament was attained by formulating the drug in both solid dispersion and physical mixture using urea and polyethylene glycol 4000 as carriers. A comparative dissolution behaviour of the medicament in different solid dispersion and physical mixture ratios were investigated at particle, size of < 63 μ. Drug-urea solid dispersion of a ratio 5:95% produced the highest dissolution rate.

Poly(Ethylene Glycol)-block-Poly(ε-Caprolactone) Nanomicelles for the Solubilization and Enhancement of Antifungal Activity of Sertaconazole

Sertaconazole nitrate is a broad spectrum imidazole antifungal agent with antibacterial and anti-inflammatory properties. However, its lipophilic nature and very poor aqueous solubility limit its use in the clinic. The aim of this study was to develop and characterize poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-b-PCL) polymeric nanomicelles for the solubilization and enhancement of sertaconazole antifungal activity. Sertaconazole was incorporated into PEG-b- PCL polymeric nanomicelles by a co-solvent evaporation method and micelle size, drug loading capacity and drug release properties were determined. The antifungal properties of nanomicelle-loaded drug were evaluated in Fusarium miscanthi, Microsporum canis, and Trichophyton mentagrophytes isolated, respectively from fungal keratitis, ringworm, and tinea corporis. PEG-b-PCL formed nanomicelles in aqueous solution with a diameter ranging from 40-80 nm, depending on the polymer composition and level of drug loading. Drug loading properties of the nanomicelles were dependent on the PCL block molecular weight and drug/polymer weight feed ratio. Drug encapsulation efficiency of up to 85% was achieved and this resulted in more than 80-fold enhancement in sertaconazole aqueous solubility at polymer concentration of 0.2%. Drug release studies showed an initial burst release followed by sustained drug release for 72 hours. In vitro antimycotic studies showed that nanomicelle-incorporated sertaconazole inhibited fungal growth in a concentration dependent manner. Further, it was more effective than the free drug in inhibiting the growth of Fusarium miscanthi and Microsporum canis. These results confirm the utility of PEG-b-PCL nanomicelles in enhancing the aqueous solubility and antifungal activity of sertaconazole or other similar antifungal drugs.

The formulation-performance relationship of multiple emulsions and ocular activity

Abstract Multiple emulsions containing prednisolone were prepared using a two step emulsification technique. The effect of various concentrations of hydrophilic and lipophilic emulsifiers (Tween-20 and Span-60) in multiple emulsions based on liquid paraffin on the drug bioavailability and duration of action as a controlled release formulation was studied following instillation in the rabbits eye. The parameter of ocular activity such as area under the intraocular pressure/time curve (AUC); time for maximum response (TMR) and half value duration (HVD) were assessed for the o/w/o and w/o/w multiple emulsions. It was found that the hydrophilic emulsifier reduced the bioavailability but increased the concentration of lipophilic emulsifier to bring about the reverse effect. Therefore the bioavailability of the drug can be controlled by the proper choice and concentration of the emulsifier in the preparation of emulsions. The hydrophile-lipophile balance (HLB) values calculated for a surfactant mixture in a multiple emulsion was found to be highly negatively correlated to the values of the parameters of ocular activity. Decreasing the HLB value of the surfactant mixture in a w/o/w emulsion favours the bioavailability; the intensity and duration of drug action.

Gold nanoparticles enhance 5-fluorouracil anticancer efficacy against colorectal cancer cells.

5-Fluorouracil (5-FU), an antimetabolite drug, is extensively used in the treatment solid tumors. However, its severe side effects limit its clinical benefits. To enhance 5-FU anticancer efficacy and reduce its side effects it was loaded onto gold nanoparticles (GNPs) using two thiol containing ligands, thioglycolic acid (TGA) and glutathione (GSH). The GNPs were prepared at different 5-FU/ligand molar ratios and evaluated using different techniques. Anticancer efficacy of 5-FU/GSH-GNPs was studied using flow cytometry in cancerous tissue obtained from patients having colorectal cancer. The GNPs were spherical in shape and had a size of ∼9-17nm. Stability of the GNPs and drug release were studied as a function of salt concentration and solution pH. Maximum 5-FU loading was achieved at 5-FU/ligand molar ratio of 1:1 and 2:1 for TGA-GNPs and GSH-GNPs, respectively. GNPs coating with pluronic F127 improved their stability against salinity. 5-FU release from GNPs was slow and pH-dependent. 5-FU/GSH-GNPs induced apoptosis and stopped the cell cycle progression in colorectal cancer cells. They also had a 2-fold higher anticancer effect compared with free 5-FU. These results confirm the potential of GNPs to enhance 5-FU anticancer efficacy.

Formulation and evaluation of metoclopramide solid lipid nanoparticles for rectal suppository

The purpose of this study was to formulate and characterize metoclopramide solid lipid nanoparticles (MCP‐SLNs) and incorporating it into suppository bases for treatment of nausea and vomiting, produced with chemotherapeutic agents, using one dose per day.

In Vivo performance of ophthalmic preparations of betamethasone and phenylephrine hydrochloride in the rabbit eye: Effect of polyvinyl alcohol.

The effect of different concentrations of polyvinyl alcohol 14000 and 72000 (PVA 14 and 72) on the activity of betamethasone and phenylephrine hydrochloride in the rabbit eye was investigated. The polymer of higher molecular weight exerts a more pronounced effect at relatively lower viscosities. Effects on the intraocular pressure are more responsive to changes in viscosity than those on pupillary response.

In vitro release study of betamethasone and phenylephrine hydrochloride from ophthalmic preparations

Abstract The in vitro release of betamethasone and phenylephrine hydrochloride from ophthalmic solutions and gels was investigated. Linearization of release data of either drug or their combination was attempted according to zero-order, first-order and diffusion kinetics. The data obtained are directly in favour of a first-order mechanism both for betamethasone and phenylephrine hydrochloride and they show that the mechanism of drug release from solutions containing viscolizers or from hydrogels is independent of the nature of the drug in terms of its water solubility or ionization. The type of polymer or the increase in viscosity of the ophthalmic preparation do not indicate the release mechanism to any significant extent. The release rate constants of phenylephrine hydrochloride are consistently higher than those of betamethasone. The preparation based on carbomer is the only exception to this. The release rate constant of the drug is highly dependent on the viscosity of the ophthalmic solution. Below the critical viscosity of 5 cp a considerable lowering of the release rate constant takes place. In ophthalmic gel the release rate constant of either drug shows a very low dependency on the basic viscosity of the gel.

Fluorouracil-Loaded Gold Nanoparticles for the Treatment of Skin Cancer: Development, in Vitro Characterization, and in Vivo Evaluation in a Mouse Skin Cancer Xenograft Model

Fluorouracil (5-FU) is an antimetabolite drug used in the treatment of various malignancies, such as colon and skin cancers. However, its systemic administration results in severe side effects. Topical 5-FU delivery for the treatment of skin cancer could circumvent these shortcomings, but it is limited by the drug poor permeability through the skin. To enhance 5-FU efficacy against skin cancer and reduce its systemic side effects, it was loaded into a gold nanoparticle (GNP)-based topical delivery system. 5-FU was loaded onto GNPs capped with CTAB through ionic interactions between 5-FU and CTAB. GNPs were prepared at different 5-FU/CTAB molar ratios and evaluated using different techniques. GNP stability and drug release were studied as a function of salt concentration and solution pH. Optimum 5-FU/CTAB-GNPs were incorporated into gel and cream bases, and their ex vivo permeability was evaluated in mice dorsal skin. The in vivo anticancer efficacy of the same preparations was evaluated in A431 tumor-bearing mice. The GNPs had spherical shape and a size of ∼16-150 nm. Maximum 5-FU entrapment was achieved at 5-FU/CTAB molar ratio of 1:1 and pH 11.5. Drug release from GNPs was sustained and pH-dependent. 5-FU GNP gel and cream had around 2-fold higher permeability through mice skin compared with free 5-FU gel and cream formulations. Further, in vivo studies in a mouse model having A431 skin cancer cells implanted in the subcutaneous space showed that the GNP gel and cream achieved 6.8- and 18.4-fold lower tumor volume compared with the untreated control, respectively. These results confirm the potential of topical 5-FU/CTAB-GNPs to enhance drug efficacy against skin cancer.

An Ion Pairing Approach to Enhance Oral Bioavailability of Alendronate

Aim: Alendronate (AL) is a nitrogen-containing bisphosphonate drug that exhibits limited oral bioavailability due to predominantly hydrophilic molecular properties. To enhance oral absorption of this important osteoporosis drug, a novel ion-pairing strategy using the cationic polymer polyethylenimine (PEI) was explored as an initial step of an alternate oral drug delivery strategy that attempts to prepare polymer-encapsulated ion pair nanoparticles. Methodology: Electrostatically stabilized AL/PEI association complexes were fabricated by combining AL and PEI solutions prepared in 0.05 M acetate buffer, pH 5.0, at different AL/PEI Short Research Article El-Hamid et al.; JSRR, 5(4): 344-351, 2015; Article no.JSRR.2015.101 345 charge ratios under stirring. The free fraction of AL after complexation with PEI was quantified spectrophotometrically at λ=300 nm using ferric chloride. Particle size distribution and zeta potential of ion pairs formed at different molar AL/PEI ratios were measured by dynamic laser light scattering. Results: The complexation efficiency of PEI was low until an AL/PEI charge ratio of1:1.7. Increasing PEI concentrations effectively decreased the free fraction of AL implying formation of stable ion pairs between the negatively charged AL and the positively charged polymer. The lowest fraction of free AL was 18.7% measured at an AL/PEI charge ratio of 1:33. The mean hydrodynamic diameter of nanoassemblies decreased with increasing AL/PEI charge ratio reaching a limiting value of 71±1.4 nm at AL/PEI=1:33. Corresponding zeta potential measured for these association complexes was +37±2.8 mV. Conclusion: AL/PEI charge ratio greater than 1:1.7 facilitates effective formation of electrostatically stabilized ion pairs that carry a significant positive surface charge indicative of substantial colloidal stability in aqueous solution. The small size of AL/PEI complexes fabricated at 1:33 favors these ion pairs for subsequent encapsulation into biocompatible polymers suitable for oral drug delivery.