Syed Nisar Hussain Shah

Formulation and evaluation of natural gum-based sustained release matrix tablets of flurbiprofen using response surface methodology

Background: This research work was done to design oral sustained release matrix tablets of water-insoluble drug, flurbiprofen, using natural gums as the matrix polymers and to evaluate the drug release characteristics using response surface methodology. The central composite design for two factors at five levels each was employed to systematically optimize drug release profile. Method: Matrix tablets were prepared by direct compression technique. Xanthan and acacia gums were taken as the independent variables. Fourier transform infrared spectroscopy studies were also performed to find out the stability of drug during the direct compression and to check the interactions between polymers and drug. Percent drug release in 2 hours and percent drug release in 8 hours were taken as response variables (Y1 and Y2, respectively). Results: Both the polymers were found to have significant effect on the drug release. Polynomial mathematical models, generated for the response variables using multiple linear regression analysis, were found to be statistically significant (P < 0.05). Contour plots were drawn to depict the relationship between response variables and independent variables. Conclusion: The formulated matrix tablets followed zero-order kinetics with negligible drug release in 0.1 N HCl at pH 1.2, which was the objective of this study to produce a formulation avoiding the gastric effects of flurbiprofen.

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.

Assessment of Eco-Friendly Natural Antimicrobial Textile Finish Extracted from Aloe Vera and Neem Plants

*Faculty of Pharmacy, Bahauddin Zakariya University, 60800 Multan, Pakistan E-mail: engr.furqan@bzu.edu.pk Abstract The aim of the present work was to assess an eco friendly natural antimicrobial textile finish extracted from Aloe gel and Neem plants. Extracted Aloe gel and active substance of Neem were mixed in a mordant to form a finish. Bleached cotton samples were treated with 5, 7, and 10% concentrations of Aloe gel and Neem separately. The same samples were then treated with a hybrid combination of Aloe gel and Neem (HCAN) extracts having 5, 7 and 10% concentrations. These finished samples were subjected to an antibacterial activity test against E. coli and S. aureus, an antifungal activity test against Aspergillus Niger, and a test of their durability of antibacterial finish fastness to washing by standard test methods. It was found that the hybrid combination of Aloe gel and Neem (HCAN) was an effective antibacterial and antifungal agent as compared to Aloe gel and Neem separately. It also showed good durability to washing.

SUSTAINED RELEASE HYDROPHILIC MATRICES BASED ON XANTHAN GUM AND HYDROXYPROPYL METHYLCELLULOSE: DEVELOPMENT, OPTIMIZATION, IN VITRO AND IN VIVO EVALUATION

Hydrophilic matrices of xanthan gum and hydroxypropyl methylcellulose were prepared by direct compression using diclofenac sodium as model drug. All formulations were subjected to physical tests, FTIR studies and dissolution studies at pH 1.2 and 6.8, to evaluate drug release kinetics. In vivo studies were carried out in rabbits using single latin cross over design and pharmacokinetic parameters were analyzed by using one way ANOVA and LSD. Physical parameters of all formulations were within limits with stability of drug during direct compression and absence of drug polymer interaction as evident by FTIR spectra. In vitro release studies showed that both polymers were able to retard the drug release but matrices containing XG showed initial greater burst release in acidic media (pH 1.2) which was absent in HPMC matrices due to delayed hydration and pH independent gelling mechanism in HPMC. XG matrices showed greater sustained release pattern in phosphate buffer solution (pH 6.8) over twenty-four hours of study due to formation of gel and viscous solution around matrices. All the formulation followed Higuchi kinetics and Korsmeyer-Peppas equation confirms the involvement of multiple drug release mechanisms release from hydrophilic matrices. Plasma drug concentration in rabbits after oral administration was used to calculate different pharmacokinetic parameters, which showed the inverse relationship of the AUC, AUMC and Cmax of the drug with polymer concentrations. Statistical evaluation confirms the role of polymer concentration on delayed release. XG matrices demonstrated fewer time to reach Tmax, higher Cmax and AUC0-∞ values as compared to batches formulated with HPMC, owing to burst release of drug from XG matrices in acidic media. Both formulations showed poor IVIVC due to in vitro and in vivo difference of pH and ionic strength.

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.

Formulation Study of Topically Applied Lotion: In Vitro and In Vivo Evaluation

INTRODUCTION This article presents the development and evaluation of a new topical formulation of diclofenac diethylamine (DDA) as a locally applied analgesic lotion. METHODS To this end, the lotion formulations were formulated with equal volume of varying concentrations (1%, 2%, 3%, 4%; v/v) of permeation enhancers, namely propylene glycol (PG) and turpentine oil (TO). These lotions were subjected to physical studies (pH, viscosity, spreadability, homogeneity, and accelerated stability), in vitro permeation, in vivo animal studies and sensatory perception testing. In vitro permeation of DDA from lotion formulations was evaluated across polydimethylsiloxane membrane and rabbit skin using Franz cells. RESULTS It was found that PG and TO content influenced the permeation of DDA across model membranes with the lotion containing 4% v/v PG and TO content showed maximum permeation enhancement of DDA. The flux values for L4 were 1.20±0.02 μg.cm(-2).min(-1) and 0.67 ± 0.02 μg.cm(-2).min(-1) for polydimethylsiloxane and rabbit skin, respectively. Flux values were significantly different (p < 0.05) from that of the control. The flux enhancement ratio of DDA from L4 was 31.6-fold and 4.8-fold for polydimethylsiloxane and rabbit skin, respectively. In the in vivo animal testing, lotion with 4% v/v enhancer content showed maximum anti-inflammatory and analgesic effect without inducing any irritation. Sensatory perception tests involving healthy volunteers rated the formulations between 3 and 4 (values ranging between -4 to +4, indicating a range of very bad to excellent, respectively). CONCLUSION It was concluded that the DDA lotion containing 4% v/v PG and TO exhibit the best performance overall and that this specific formulation should be the basis for further clinical investigations.

Permeation Kinetics Studies of Physical Mixtures of Artemisinin in Polyvinylpyrrolidone

Artemisinin (ART), the parent compound of a novel family of antimalarial drugs, was used as a model drug that is lipophilic and has low bioavailability (32%) after oral delivery. The primary objective was to study the effect of polyvinylpyrrolidone (PVP) on the permeation enhancement and solubility of physical mixtures (PM) of ART in PVP–K30 in various solvent systems (i.e., distilled water, phosphate buffered saline [PBS], and methanol). PMs of drug–PVP in 1:0.5, 1:1, 1:2, 1:4, and 1:9 ratios were prepared by simple mixing in a mortar and pestle. Fourier transform infrared (FTIR) spectrophotometry and X-ray powder diffraction (XRPD) were applied to characterize the PMs. The solubility of ART was investigated at 37 ± 0 .5 ° C in three solvents. Permeation of ART-saturated solutions across a silicone membrane in Franz diffusion cells was studied using Fick’s law of diffusion. FTIR and XRPD studies have shown some interactions, and there was a phase change of artemisinin from crystalline to amorphous form as the concentration of PVP–K30 in PM ratios increased. Solubility order increased with an increase in PVP– K30 concentration for the water–PBS solvent system, while in methanol, it was erratic. Flux rate and permeability coefficient were enhanced with an increase in PVP–K30 concentration. In less permeable solvents like water and PBS, the enhancement ratio was high, while the enhancement ratio was low in a highly permeable solvent like methanol. In conclusion, with an increase in concentration of PVP, the permeation rate and solubility of ART increased.