Yasser Shahzad

Swelling and Controlled Release of Tramadol Hydrochloride from a pH-Sensitive Hydrogel

In the present study pH-sensitive polyvinylpyrrolidone/acrylic acid (PVP/AA) hydrogels were synthesized by free radical polymerization in the presence of ethylene glycol dimethacrylate (EGDMA) as a cross-linker. For this purpose, different concentrations of PVP, AA and EGDMA were used to synthesize polymeric networks. This study focused on evaluating the effect of the composition on the swelling of hydrogels and release of tramadol hydrochloride at varying pH (1.2, 5.5, 6.5 and 7.5). Gel fraction, porosity and diffusion coefficient were also determined. The hydrogels were characterized using scanning electron microscopy for surface morphology, Fourier transform infrared spectroscopy and X-ray diffraction for studying possible chemical interactions. The hydrogels exhibited a pH-dependent swelling behavior. The degree of swelling, as well as drug release from PVP/AA hydrogel, was significantly increased as pH varied from 1.2 to 7.5. Swelling was increased by increasing the AA content, while a decrease in swelling was observed with increasing EGDMA content. Drug-release data were fitted to kinetic models including zero-order, firstorder, Higuchi and Korsmeyer–Peppas. Results indicated that release of tramadol hydrochloride from the PVP/AA hydrogel was non-Fickian and that the mechanism was diffusion controlled.

Breaching the skin barrier through temperature modulations.

The impermeability of the stratum corneum often hinders the transport of molecules across the skin. Temperature modulations in the skin and the application of local heat both have the potential of circumventing this problem temporarily and reversibly and when applied, may aid in enhancing drug diffusion through the skin. A controlled and precise application of heat has the ability to create a cascade of events in the skin and thus aids in facilitating a faster movement of molecules into and across the skin. Possible mechanisms of enhancing drug permeation include: a) increase in drug diffusivity in the vehicle and/or in the skin, b) increase in partitioning and diffusion, c) disturbance in the lipid structure of the stratum corneum, and d) increased local blood flow. These mechanisms may operate individually or concurrently. The creation of micropores or channels in response to exposure to very high heat energy for a fraction of time is another technique that can facilitate the transport, known as thermal ablation. These micropores then serve as channels from where drug molecules can escape from formulations into the skin at a much faster rate than through passive diffusion. This review, therefore, summarises the effects that temperature modulations may have on the permeability of the skin. Physical techniques of heat induced skin ablation, such as chemical heating, thermoporation, radiofrequency induced thermal ablation, and laser induced thermal ablation are also presented in this review.

pH-sensitive polyvinylpyrrolidone-acrylic acid hydrogels: Impact of material parameters on swelling and drug release

Trichophyton mentagrophytes is a fungus causative agent of dermatophytosis, affecting humans worldwide. This has driven the search for products for the treatment of these infections. Accordingly, the aim of this study was to investigate the antifungal activity of the Cymbopogon winterianus essential oil against T. mentagrophytes. The antifungal tests consisted of antifungal screening, determination of MIC and MFC, analysis of the essential oils effects on mycelial growth, germination of fungal spores, fungal viability, morphogenesis, cell wall (test with sorbitol) and cell membrane (cell leakage test) of T. mentagrophytes. Upon screening, the oil inhibited all strains, with zones of growth inhibition of 24-28 mm in diameter. The MIC was 312 μg/mL and CFM was 2500 μg/mL for almost all the strains tested. There were morphological changes in the conidia group, form and pigmentation of hyphae. The antifungal action of the product does not involve the cell wall and its action may involve the fungal plasma membrane. It is concluded that C. winterianus essential oil constitutes a potential antifungal product, especially for the treatment of dermatophytosis.

Development of solid dispersions of artemisinin for transdermal delivery

Solid dispersions of the poorly soluble drug artemisinin were developed using polymer blends of polyvinylpyrrolidone (PVP) and polyethylene glycol (PEG) with the aim of enhancing solubility and in vitro permeation of artemisinin through skin. Formulations were characterised using a combination of molecular dynamics (MD) simulations, differential scanning calorimetry (DSC), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR). Solubility of artemisinin was determined in two solvents: de-ionised water and phosphate buffered saline (PBS; pH 7.4), while in vitro drug permeation studies were carried out using rabbit skin as a model membrane. MD simulations revealed miscibility between the drug and polymers. DSC confirmed the molecular dispersion of the drug in the polymer blend. Decrease in crystallinity of artemisinin with respect to polymer content and the absence of specific drug-polymer interactions were confirmed using XRD and FT-IR, respectively. The solubility of artemisinin was dramatically enhanced for the solid dispersions, as was the permeation of artemisinin from saturated solid-dispersion vehicles relative to that from saturated solutions of the pure drug. The study suggests that high energy solid forms of artemisinin could possibly enable transdermal delivery of artemisinin.

Characterization of Ethylcellulose and Hydroxypropyl MethylcelluloseMicrospheres for Controlled Release of Flurbiprofen

Characterization of Ethylcellulose and Hydroxypropyl Methylcellulose Microspheres for Controlled Release of Flurbiprofen The objective of this study was to design and optimize polymeric microspheres of flurbiprofen (FLB) with ethylcellulose (EC) and hydroxypropyl methylcellulose (HPMC) using response surface methodology. EC and HPMC were taken as independent variables whereas; the dependent variables were % drug release at pH 1.2, 4.5 and 7.4. FTIR spectra and TGA showed no significant difference between drug and polymers. DSC and XRD studies exhibited molecular dispersion of FLB within microspheres. Contour plots were drawn to predict the relationship between dependent and independent variables. Both polymers revealed their significant effects on drug release that followed the zero order which was further verified by the lowest values of Akaike information criterion. The mechanism of drug release followed super case II type of drug release. This study helped unraveling the influence of two factors on in-vitro drug release and thereby, proposed an appropriate sustained drug release formulation.

Applying response surface methodology to optimize nimesulide permeation from topical formulation.

Nimesulide is a non-steroidal anti-inflammatory drug that acts through selective inhibition of COX-2 enzyme. Poor bioavailability of this drug may leads to local toxicity at the site of aggregation and hinders reaching desired therapeutic effects. This study aimed at formulating and optimizing topically applied lotions of nimesulide using an experimental design approach, namely response surface methodology. The formulated lotions were evaluated for pH, viscosity, spreadability, homogeneity and in vitro permeation studies through rabbit skin using Franz diffusion cells. Data were fitted to linear, quadratic and cubic models and best fit model was selected to investigate the influence of permeation enhancers, namely propylene glycol and polyethylene glycol on percutaneous absorption of nimesulide from lotion formulations. The best fit quadratic model explained that the enhancer combination at equal levels significantly increased the flux and permeability coefficient. The model was validated by comparing the permeation profile of optimized formulations’ predicted and experimental response values, thus, endorsing the prognostic ability of response surface methodology.

Modelling skin permeability with micellar liquid chromatography.

This study evaluates the potential application of micellar liquid chromatography (MLC) to predict skin permeation with a series of model compounds. MLC has previously been found to be useful in the prediction of partition coefficient values (logP) for pharmaceutical compounds, yet has not been incorporated in skin permeability models prior to this work. This article provides statistically supported data that this technique enhances the ability to predict the permeability of similar drugs through the skin (K(p)). The replacement of a traditional physicochemical parameter, namely the octanol-water partition coefficient (logP(ow)) with a chromatographically determined value (logP(mw)), results in a quantitative partition-permeability relationship that is robust to variation. MLC offers many benefits compared with the traditional techniques employed to obtain logP values.

Chemically Cross-Linked Poly(acrylic-co-vinylsulfonic) Acid Hydrogel for the Delivery of Isosorbide Mononitrate

We report synthesis, characterization, and drug release attributes of a series of novel pH-sensitive poly(acrylic-co-vinylsulfonic) acid hydrogels. These hydrogels were prepared by employing free radical polymerization using ethylene glycol dimethacrylate (EGDMA) and benzyl peroxide (BPO) as cross-linker and initiator, respectively. Effect of acrylic acid (AA), polyvinylsulfonic acid (PVSA), and EGDMA on prepared hydrogels was investigated. All formulations showed higher swelling at high pHs and vice versa. Formulations containing higher content of AA and EGDMA show reduced swelling, but one with higher content of PVSA showed increased swelling. Hydrogel network was characterized by determining structural parameters and loaded with isosorbide mononitrate. FTIR confirmed absence of drug polymer interaction while DSC and TGA demonstrated molecular dispersion of drug in a thermally stable polymeric network. All the hydrogel formulations exhibited a pH dependent release of isosorbide mononitrate which was found to be directly proportional to pH of the medium and PVSA content and inversely proportional to the AA contents. Drug release data were fitted to various kinetics models. Results indicated that release of isosorbide mononitrate from poly(AA-co-VSA) hydrogels was non-Fickian and that the mechanism was diffusion-controlled.

Influence of cellulose derivative and ethylene glycol on optimization of lornoxicam transdermal formulation

Lornoxicam containing topically applied lotions were formulated and optimized with the aim to deliver it transdermally. The formulated lotions were evaluated for pH, viscosity and in vitro permeation studies through silicone membrane using Franz diffusion cells. Data were fitted to linear, quadratic and cubic models and best fit model was selected to investigate the influence of variables, namely hydroxypropyl methylcellulose (HPMC) and ethylene glycol (EG) on permeation of lornoxicam from topically applied lotion formulations. The best fit quadratic model revealed that low level of HPMC and intermediate level of EG in the formulation was optimum for enhancing the drug flux across silicone membrane. FT-IR analysis confirmed absence of drug-polymer interactions. Selected optimized lotion formulation was then subjected to accelerated stability testing, sensatory perception testing and in vitro permeation across rabbit skin. The drug flux from the optimized lotion across rabbit skin was significantly better that that from the control formulation. Furthermore, sensatory perception test rated a higher acceptability while lotion was stable over stability testing period. Therefore, use of Box-Wilson statistical design successfully elaborated the influence of formulation variables on permeation of lornoxicam form topical formulations, thus, helped in optimization of the lotion formulation.

The evaluation of coated granules to mask the bitter taste of dihydroartemisinin

O objetivo deste estudo foi o de mascarar o gosto amargo caracteristico da diidroartemisinina (DHA) pelo uso de diferentes materiais de revestimento. Experimento-1 e experimento-2 foram realizados para preparar grânulos de DHA. Os grânulos produzidos pelo experimento-1 mostraram-se irregulares e menores se comparados aos obtidos pelo experimento-2, que foram mais regulares e maiores. Os grânulos obtidos em ambos os experimentos foram, entao, revestidos por dois metodos distintos de revestimento, designados como A e B, dependendo do material de revestimento empregado. Os grânulos do experimento-2 mostraram melhor propriedade de fluxo que os obtidos no experimento-1. Estudos de dissolucao in vitro em tampao fosfato pH 6,8 revelaram que grânulos do experimento-2B liberaram apenas 34% ± 3 da DHA em dois minutos se comparado com experimento-1A (57% ± 2), experimento-1B (48% ± 2) e experimento-2A (53% ± 7). A Analise Sensorial quanto ao sabor (Pleasant Taste Perception - PTP) tambem confirmou a eficacia do experimento-2B (P <0,05) em mascarar o gosto amargo da DHA. Microscopia Eletronica de Varredura (SEM) revelou a superficie mais regular e lisa dos grânulos obtidos pelo experimento-2B. Alem disso, Analise Termogravimetrica e Analise Termica Diferencial (TG-DTA) confirmaram que nao ha nenhuma interacao entre os materiais e a DHA pura. DHA mostrou seus picos caracteristicos na Difracao de Raios X (XRD) em padroes que tambem foram proeminentes em todas as amostras. Em conclusao, os grânulos obtidos pelo experimento-2B exibiram diminuicao consideravel no gosto amargo da DHA, o que era o proposito deste estudo.