Rana M. Obaidat

Controlled release of tramadol hydrochloride from matrices prepared using glyceryl behenate

An inert matrix to control the release of tramadol HCl was prepared using glyceryl behenate as a matrix-forming agent. The matrices were prepared by either direct compression of a physical mixture of the drug and the matrix-forming agent or by compression of granules prepared by hot fusion of the drug and the matrix-forming agent. The hot fusion method was found to be more effective than compression of physical mixtures in retarding the release of the drug from the matrix. Drug release was adjusted by using release enhancers, such as microcrystalline cellulose and lactose, and the results showed that higher release rates were obtained using lactose. However, the release of the drug was independent of the compression force and the pH of the dissolution medium. This study showed that glyceryl behenate is an appropriate waxy material that can be used as a matrix-forming agent to control the release of a water-soluble drug such as tramadol HCl.

Preparation of mucoadhesive oral patches containing tetracycline hydrochloride and carvacrol for treatment of local mouth bacterial infections and candidiasis.

The specific aim of this work was to prepare mucoadhesive patches containing tetracycline hydrochloride and carvacrol in an attempt to develop a novel oral drug delivery system for the treatment of mouth infections. The bilayered patches were prepared using ethyl cellulose as a backing layer and carbopol 934 as a matrix mucoadhesive layer. Patches were prepared with different loading amounts of tetracycline hydrochloride and carvacrol. The antimicrobial activity was assessed for the prepared patches using the disc-diffusion method against the yeast Candida albicans and five bacterial strains, including Pseudomonas aeruginosa, Escherichia coli, Bacillus cereus, Staphylococcus aureus, and Bacillus bronchispti. In this work, we highlighted the possibility of occurrence of a synergistic action between carvacrol and tetracycline. The best formulation was selected based on microbiological tests, drug release, ex-vivo mucoadhesive performance, and swelling index. Physical characteristics of the selected formulations were determined. These included pH, patch thickness, weight uniformity, content uniformity, folding endurance, and patch stability.

Formulation and In Vitro Evaluation of Xanthan Gum or Carbopol 934-Based Mucoadhesive Patches, Loaded with Nicotine

Bilayer nicotine mucoadhesive patches were prepared and evaluated to determine the feasibility of the formulation as a nicotine replacement product to aid in smoking cessation. Nicotine patches were prepared using xanthan gum or carbopol 934 as a mucoadhesive polymers and ethyl cellulose as a backing layer. The patches were evaluated for their thickness, weight and content uniformity, swelling behavior, drug–polymers interaction, adhesive properties, and drug release. The physicochemical interactions between nicotine and the polymers were investigated by Fourier transform infrared (FTIR) spectroscopy. Mucoadhesion was assessed using two-arm balance method, and the in vitro release was studied using the Franz cell. FTIR revealed that there was an acid base interaction between nicotine and carbopol as well as nicotine and xanthan. Interestingly, the mucoadhesion and in vitro release studies indicated that this interaction was strong between the drug and carbopol whereas it was weak between the drug and xanthan. Loading nicotine concentration to non-medicated patches showed a significant decrease in the mucoadhesion strength of carbopol patches and no significant effect on the mucoadhesion strength of xanthan patches. In vitro release studies of the xanthan patches showed a reasonable fast initial release profile followed by controlled drug release over a 10-h period.

Determination of factors affecting kinetics of solid-state transformation of fluconazole polymorph II to polymorph I using diffuse reflectance Fourier transform spectroscopy

Background: It was of interest to investigate the factors affecting kinetics of transformation of fluconazole polymorph II (the metastable form) to fluconazole polymorph I (the stable form) using diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS). Method: Fluconazole polymorphs I and II both were prepared by crystallization in dichloromethane. The two forms were characterized using differential scanning calorimetry, thermogravimetric analysis, powder X-ray diffraction, solubility, and DRIFTS. Transformation of polymorph II to polymorph I was also studied under different isothermal temperatures using DRIFTS. Kinetic analyses of the data were done using model-dependent and model-independent methods. Eighteen solid-state reaction models were used to interpret the experimental results. Results: Based on statistics, the Prout–Tompkins model provided the best fit for the transformation. The activation energy (Ea) value derived from the rate constants of the Prout–Tompkins model was 329 kJ/mol. Model-independent analysis was also applied to the experimental results. The average values calculated using both methods were not significantly different. Factors affecting kinetics of transformation such as mechanical factors, relative humidity, and the effect of seeding were also studied. Mechanical factors, which included trituration and compression, proved to enhance transformation rate significantly. Relative humidity proved to transform both polymorphs to monohydrate form. The presence of seed crystals of polymorph I was proved not to affect the transformation process of polymorph II to polymorph I. Effect of solvent of crystallization (dichloromethane) was studied. A significant change of the rate of transformation was proved in the presence of solvent vapors, and a change on the mechanism was proposed.

Effect of processing parameters on preparation of carrageenan aerogel microparticles

The aim of this work is to produce aerogel microparticles using a biocompatible polymer. Commercial available carrageenan suitable for gelation was used as a precursor for gel preparation. Microspherical carrageenan gel particles were obtained by applying emulsion technology. The gel was converted to an aerogel using supercritical carbon dioxide extraction process. Several process parameters were investigated for their effect on the final properties of the produced aerogel. The produced aerogel particles were characterized for their textural properties using gas sorption analysis. For complete understanding the following characterization techniques were employed: FTIR, PXD, TGA, SEM, Zeta sizer, particles density and particle size distribution. In conclusion, biodegradable aerogel micro-spherical particles based on three different commercial available carrageenan were produced. Depending on the process parameters the surface area of the produced aerogel ranged between 33 and 174m2/g, the average pore volume and pore sized were 0.35±0.11cm3/g and 12.34±3.24 respectively. The produced porous material shows potential characteristic for drug delivery application.

Enhancement of levodopa stability when complexed with β-cyclodextrin in transdermal patches

Abstract Levodopa is a promising candidate for administration via the transdermal route because it exhibits a short plasma half-life and has a small window of absorption in the upper section of the small intestine. The aim of this study was to prepare stable levodopa transdermal patches. Both xanthan gum and Carbopol 971 polymers were selected with ethylcellulose constituting the backing layer of the prepared patches. The effect of adding β-cyclodextrin on the prepared patches was investigated. The uniformity in thickness, weight and content of the studied patches was acceptable. Physicochemical characterization revealed that there was no interaction between levodopa and the applied polymer. The results proved that levodopa precipitated as an amorphous form in carbopol patches. Controlled drug release was achieved for all the tested patches over a 6 h period. However, increased permeation was achieved for the carbopol patches. Although cyclodextrin did not enhance levodopa permeation, the stability study confirmed that levodopa stability was enhanced when complexed with β-cyclodextrin. The cumulative amount of drug released from carbopol patches is slightly higher than that of xanthan patches. The optimal stability was achieved in the carbopol/levodopa:β-cyclodextrin patch. The levodopa-β-cyclodextrin complex was successfully characterized using X-ray diffraction, NMR analysis and molecular dynamics simulations. In conclusion, carbopol/levodopa:β-cyclodextrin patches can be considered as a promising stable and effective transdermal drug-delivery system.

Moderate hydrostatic pressure–temperature combinations for inactivation of Bacillus subtilis spores

We report the effect of using moderate hydrostatic pressure, 40–140 MPa, at moderate temperature (38–58°C) to inactivate Bacillus subtilis spores in McIlvaines citric phosphate buffer at pH 6. We have investigated several parameters: pressure applied, holding time, pressure cycling, and temperature. The kinetics of spore inactivation is reported. The results show that spore inactivation is exponentially proportional to the time the sample is exposed to pressure. Spore germination and inactivation occur at the hydrostatic pressures/temperature combinations we explored. Cycling the pressure while keeping the total time at high pressure constant does not significantly increase spore inactivation. We show that temperature increases spore inactivation at two different rates; a slow rate below 33°C, and at a more rapid rate at higher temperatures. Increasing pressure leads to an increase in spore inactivation below 95 MPa; however, further increases in pressure give a similar rate kill. The time dependence of the effect of pressure is consistent with the first-order model (R2 > 0.9). The thermal resistance values (ZT) of B. subtilis spores are 30°C, 37°C, and 40°C at 60, 80, 100 MPa. The increase in ZT value at higher pressures indicates lower temperature sensitivity. The pressure resistance values (ZP) are 125, 125 and 143 MPa at 38°C, 48°C, and 58°C. These ZP values are lower than those reported for B. subtilis spores in the literature, which indicates higher sensitivity at pressures less than about 140 MPa. We show that at temperatures <60°C, B. subtilis spores are inactivated at pressures below 100 MPa. This finding could have implications for the design of the sterilization equipment.

Effect of different polymeric dispersions on In-vitro dissolution rate and stability of celecoxib class II drug

Solid dispersions can play a significant role in the enhancement of drug dissolution and stability. Still, the polymeric effect can vary according to the possibility of intermolecular forces with the drug. The objective of this study was to evaluate the effect of several polymers on enhancement in-vitro dissolution behavior of celecoxib; in addition to comparing prepared dispersions with selected commercial products. Solid dispersions of celecoxib were prepared with different ratios between the drug and selected polymer (Soluplus®, polyvinyl pyrrolidine, Chitosan, polyethylene glycol). Physicochemical characterizations were performed using Powder X-ray diffraction, Differential Scanning Calorimetry, Fourier Transform Infra-Red analysis and Scanning Electron Microscopy. Dispersions were subjected to in-vitro drug release studies. Results revealed enhancement in dissolution rate for all dispersions prepared except for Chitosan-based dispersions that showed clear retardation in the drug release. Prepared dispersions from other polymers succeeded to match with release profile of two commercially marketed products (Celebrex® and Flamex®). Further Characterization of Chitosan dispersions revealed presence celecoxib in its crystalline form entrapped inside Chitosan carrier with the presence of two hydrogen bonding between Chitosan and celecoxib. Although both Polyvinylpyrrolidone, and polyethylene glycol dispersions showed a great enhancement in drug release; both failed to maintain stability. Sticky paste formation occurred to dispersions, and recrystallization took place in polyethylene glycol dispersions.

Significant solubility of carbon dioxide in Soluplus® facilitates impregnation of ibuprofen using supercritical fluid technology

Abstract Treatment of Soluplus® with supercritical carbon dioxide allows promising applications in preparing dispersions of amorphous solids. Several characterization techniques were employed to reveal this effect, including CO2 gas sorption under high pressure and physicochemical characterizations techniques. A gravimetric method was used to determine the solubility of carbon dioxide in the polymer at elevated pressure. The following physicochemical characterizations were used: thermal analysis, X-ray diffraction, Fourier transform, infrared spectroscopy and scanning electron microscopy. Drug loading of the polymer with ibuprofen as a model drug was also investigated. The proposed treatment with supercritical carbon dioxide allows to prepare solid solutions of Soluplus® in less than two hours at temperatures that do not exceed 45 °C, which is a great advantage to be used for thermolabile drugs. The advantages of using this technology for Soluplus® formulations lies behind the high sorption capability of carbon dioxide inside the polymer. This will ensure rapid diffusion of the dissolved/dispersed drug inside the polymer under process conditions and rapid precipitation of the drug in the amorphous form during depressurization accompanied by foaming of the polymer.

Investigation of Carrageenan Aerogel Microparticles as a Potential Drug Carrier

Carrageenan is an anionic polysaccharide offering many advantages to be used in drug delivery applications. These include availability, thermo-stability, low toxicity, and encapsulating properties. Combination of these properties with aerogel properties like large surface area and porosity make them an ideal candidate for drug adsorption and delivery applications. Emulsion-gelation technique was used to prepare carrageenan gel microparticles with supercritical CO2 for drying and loading purposes. Ibuprofen has been selected as a model drug for drug loading inside. The prepared microparticles were characterized using particle size analysis, X-ray diffraction, differential scanning calorimetry, Fourier transform infrared spectroscopy, density measurements, surface area, and porosity measurements. Finally, dissolution was applied to the loaded preparations to test in vitro drug release. Ibuprofen was successfully loaded in the amorphous form inside the prepared microparticles with a significant enhancement in the drug release profile. In conclusion, prepared carrageenan aerogel microparticles showed an excellent potential for use as a drug carrier.