Ibrahim A. Alsarra

Chitosan topical gel formulation in the management of burn wounds

Wound healing properties of chitosan with different molecular weight and degree of deacetylation ranges have been examined. The macroscopic image and histopathology were examined using chitosan, Fucidin ointment and to blank. The rate of contraction was evaluated by determination of the unclosed area as a function of time. The treated wounds were found to contract at the highest rate with high molecular weight-high degree of deacetylation chitosan-treated rats as compared to untreated, treated, and Fucidin ointment-treated rats. Wounds treated with high molecular weight chitosan had significantly more epithelial tissue (p<0.05) than wounds with any other treatment and the best re-epithelization and fastest wounds closure were found with the high molecular weight chitosan treatment group. Histological examination and collagenase activity studies revealed advanced granulation tissue formation and epithelialization in wounds treated with high molecular weight chitosan (p<0.05). High molecular weight with high degree of deacetylation chitosan samples therefore demonstrates potential for use as a treatment system for dermal burns.

Micromatricial Metronidazole Benzoate Film as a Local Mucoadhesive Delivery System for Treatment of Periodontal Diseases

The main objective of this study was to develop a local, oral mucoadhesive metronidazole benzoate (MET) delivery system that can be applied and removed by the patient for the treatment of periodontal diseases. Mucoadhesive micromatricial chitosan/poly(ε-caprolactone) (CH/PCL) films and chitosan films were prepared. thermal behavior, morphology, and particle size measurements were used to evaluate the prepared films. The effect of different molar masses of CH and different ratios of medium Mwt molar mass chitosan (MCH):PCL on water absorption, in vitro bioadhesion, mechanical properties, and in vitro drug release was examined. In vivo performance of the selected formulation was also evaluated. Differential scanning calorimetry examination revealed that MET existed mainly in amorphous form. Under microscopic examination, PCL microparticles were homogeneously dispersed in the films. The use of different molar masses of CH and different ratios of (MCH):PCL affected the size of the entrapped particles. Addition of PCL significantly decreased percentage water uptake and bioadhesion force compared with pure CH film. With regard to mechanical properties, the 2-layered film containing 1∶0.625 MCH:PCL had the best tensile properties. At fixed CH:PCL ratio (1∶1.25), the slowest drug release was obtained from films containing high molar mass CH. On the other hand, the 2-layered film that consisted of 1∶0.625 MCH:PCL had the slowest MET release. In vivo evaluation of the selected film revealed that metronidazole concentration in saliva over 6 hours ranged from 5 to 15 μg/mL, which was within and higher than the reported range of minimum inhibitory concentration for metronidazole. A significant in vitro/in vivo correlation under the adopted experimental conditions was obtained.

Nanoemulsions as potential vehicles for transdermal and dermal delivery of hydrophobic compounds: an overview

Introduction: In recent years, nanoemulsions have been investigated as potential drug delivery vehicles for transdermal and dermal delivery of many compounds especially hydrophobic compounds in order to avoid clinical adverse effects associated with oral delivery of the same compounds. Droplet size and surface properties of nanoemulsions play an important role in the biological behavior of the formulation. Areas covered: In this review, current literature of transdermal and dermal delivery of hydrophobic compounds both in vitro as well as in vivo has been summarized and analyzed. Expert opinion: Nanoemulsions have been formulated using a variety of pharmaceutically acceptable excipients. In many cases of dermal and transdermal nanoemulsions, the skin irritation or skin toxicity issues on human beings have not been considered which needs to be evaluated properly. In the last decade, much attention has been made in exploring new types of nanoemulsion-based drug delivery system for dermal and transdermal delivery of many hydrophobic compounds. This area of research would be very advantageous for formulation scientists in order to develop some nanoemulsion-based formulations for their commercial exploitation and clinical applications.

The use of spray-drying to enhance celecoxib solubility

The present research investigates the enhancement of the dissolution rate of celecoxib by using spray-drying to prepare a solid dispersion with various polymers, namely Kollicoat IR® (Kollicoat), polyvinyl alcohol (PVA) 22000, or polyethylene glycol 6000 (PEG). The investigated drug-to-polymer mass ratios were 1:1, 1:2, and 1:4 by weight. Hydroalcoholic or methylene chloride solvent systems were used. The obtained yields ranged from 65% to 78%, whereas the entrapment efficiencies were between 68% and 82%. The results revealed an increase in the dissolution rate of the prepared particles up to 200% within 20 min. The prepared particles were investigated using differential scanning calorimetry, scanning electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy. The increased dissolution rate was attributed to hydrogen bond formation between celecoxib and each polymer together with the reduced size of the formed particles offering a greater overall surface area. It was concluded that spray-drying may be considered a successful one-step technique to improve the dissolution rate of celecoxib when using Kollicoat, PVA, or PEG as the carrier polymer.

Mucoadhesive Polymeric Hydrogels for Nasal Delivery of Acyclovir

The study evaluated different mucoadhesive polymeric hydrogels for nasal delivery of acyclovir. Gels containing poly-N-vinyl-2-pyrrolidone (PVP) were prepared with crosslinking achieved by irradiation with a radiation dose of 15 kGy being as efficient as 20 kGy. Gels containing chitosan and carbopol were also evaluated. The mucoadhesive properties of gels were measured by a modification of a classical tensile experiment, employing a tensile tester and using freshly excised sheep nasal mucosa. Considering the mucoadhesive force, chitosan gel and gel prepared with 3% PVP in presence of polyethylene glycol (PEG) 600 were the most efficient. The in vitro drug release depended on the gel composition. Higher release rates were obtained from PVP gels compared to chitosan or carbopol gels. The release rate of drug from PVP gels was increased further in presence of PEG or glycerol. Histopathological investigations proved that the PVP was a safe hydrogel to be used for mucosal delivery. The PEG in gel formulations caused less damages to the nasal mucosal compared to formulation containing glycerol.

Testosterone solid lipid microparticles for transdermal drug delivery. Formulation and physicochemical characterization

Purpose: The main objective of the study was to formulate and characterize testosterone (TS) solid lipid microparticles (SLM) to be applied as a transdermal delivery system. Methods: Testosterone SLMs were formulated using an emulsion melt homogenization method. Various types and concentrations of fatty materials, namely glyceryl monostearate (GM), glyceryl distearate (GD), stearic acid (SA) and glyceryl behanate (GB) were used. The formulations contained 2.5 or 5 mg TS g−1. Morphology, particle size, entrapment efficiency (EE), rheological properties and thermal behaviour of the prepared SLM were examined. In vitro release characteristics of TS from various prepared SLM were also evaluated over 24 h using a vertical Franz diffusion cell. In addition, the effect of storage and freeze-drying on particle size and release pattern of TS from the selected formulation was evaluated. Results: The results indicated that the type of lipid affected the morphology and particle size of SLM. A relatively high drug percentage entrapment efficiency ranging from 80.7–95.7% was obtained. Rheological studies showed plastic flow characteristics of the prepared formulations. DSC examination revealed that TS existed in amorphous form in the prepared SLM. Release studies revealed the following rank order of TS permeation through cellophane membrane after application of various formulations: 5% GM < 5% GD < 5% SA < 5% GB < 2.5% GM < 2.5% SA < 10% GD < 10% GB. The drug permeation through excised abdomen rat skin after application of 10% GB–2.5 mg TS g−1 SLM was lower than that permeated through cellophane membrane. Moreover, SLM containing 10% GB–2.5 mg TS g−1 stored at 5°C showed good stability as indicated by the release study and particle size analysis. Trehalose showed high potential as a cryoprotectant during freeze drying of the selected SLM formulation. Conclusions: The developed TS SLM delivery system seemed to be promising as a TS transdermal delivery system.

Acyclovir Liposomes for Intranasal Systemic Delivery: Development and Pharmacokinetics Evaluation

Intranasal route is one of the most attractive routes for distributing drugs to systemic circulation. Liposomes are used as biocompatible carriers to improve delivery properties across nasal mucosa. The objective of the present study was to formulate acyclovir liposomes and partition into poly-N-vinyl-2-pyrrolidone. Entrapment efficiency showed that multilamellar and unilamellar liposomes were 43.2% ± 0.83 and 21% ± 1.01, respectively. The bioavailability of acyclovir from nasal mucoadhesive gel was 60.72% compared with intravenous route. The use of liposomes acyclovir and mucoadhesive gel not only promoted the prolonged contact between the drug and the absorptive sites in the nasal cavity, but also facilitated direct absorption through the nasal mucosa.

Transdermal Delivery of Tadalafil. I. Effect of Vehicles on Skin Permeation

Transdermal delivery that avoids the presystemic disposition can provide an alternative to oral administration of tadalafil. Accordingly, the aim of this study was to select the best vehicle as the first step in optimization of tadalafil transdermal delivery. The vehicles were used neat or in selected binary combinations and were evaluated for drug solubilization and transdermal delivery. The drug solubility in pure vehicles were ranked as polyethylene glycol (PEG) 400 > propylene glycol (PG) > ethanol > ethyl oleate (EO) > isopropyl myristate (IPM) > water. The solubility in binary systems containing ethanol at 2:1 ratios with EO or IPM was greater than that obtained with pure ethanol, EO, or IPM. This effect could be due to the cosolvency effect. The transdermal drug delivery from pure vehicles was ranked as IPM > EO > ethanol > PG > PEG > water. The delivery from binary mixtures of ethanol with either IPM or EO was higher than that obtained from pure solvents with the delivery increasing with increasing ethanol concentration in the mixtures. The delivery from binary mixtures was synergistic rather than additive. The study thus demonstrated a potential of tadalafil transdermal delivery. Binary combinations of ethanol with either IPM or EO provided the first step forward toward the development of transdermal delivery system for tadalafil.

Preparation and Characterization of Spironolactone-Loaded Gelucire Microparticles Using Spray-Drying Technique

The basic objectives of this study were to prepare and characterize solid dispersions of poorly soluble drug spironolactone (SP) using gelucire carriers by spray-drying technique. The properties of the microparticles produced were studied by differential scanning calorimetry (DSC), scanning electron microscopy, saturation solubility, encapsulation efficiency, and dissolution studies. The absence of SP peaks in DSC profiles of microparticles suggests the transformation of crystalline SP into an amorphous form. The in vitro dissolution test showed a significant increase in the dissolution rate of microparticles as compared with pure SP and physical mixtures (PMs) of drug with gelucire carriers. Therefore, the dissolution rate of poorly water-soluble drug SP can be significantly enhanced by the preparation of solid dispersion using spray-drying technique.

Microwave Irradiation-Assisted Synthesis of a Novel Crown Ether Crosslinked Chitosan as a Chelating Agent for Heavy Metal Ions (M +n )

Microwave irradiation was used to obtain a di-Schiff base type crosslinked chitosan dibenzocrown ether (CCdBE) via the reaction between the –NH2 and –CHO groups in chitosan and 4,4′-diformyldibenzo-18-c-6, respectively. The structure of the synthesized compound was characterized by elemental analysis, solid state 13C-NMR and FT-IR spectra analysis. The results showed that the mass fraction of nitrogen in the CCdBE derivative was much lower than those of chitosan. The FT-IR spectra of CCdBE revealed the expected chitosan-crown ether structure, as evidenced by the presence of the characteristic C=N and Ar peaks. The adsorption properties of CCdBE for Pd2+ and Hg2+ were investigated and the results demonstrated that the adsorbent has both desirable adsorption properties with a high particular adsorption selectivity for Hg2+ when in the presence of Pb2+ as well as selectivity coefficients for metal ions of KHg2+/Pb2+ = 8.00 and KHg2+/Pb2+ = 10.62 at pH values of 4 and 6, respectively. The reusability tests for CCdBE for Pb2+ adsorption showed that complete recovery of the ion was possible with CCdBE after 10-multiple reuses while CTS had no reusability at acidic solution because of its higher dissolution. The studied features of CCdBE suggested that the material could be considered as a new adsorbent. It is envisaged that the crosslinking of CTS into CCdBE would enhance practicality and effectiveness of adsorption in ion separation and removal procedures.