In the present study, midazolam (MDZ)-loaded chitosan nanoparticle formulation was investigated f... more In the present study, midazolam (MDZ)-loaded chitosan nanoparticle formulation was investigated for enhanced transport to the brain through the intranasal (IN) route. These days, IN MDZ is very much in demand for treating life-threatening seizure emergencies; therefore, its nanoparticle formulation was formulated in the present work because it could substantially improve its brain targeting via the IN route. MDZ-loaded chitosan nanoparticles (MDZ-CSNPs) were formulated and optimized by the ionic gelation method and then evaluated for particle size, particle size distribution (PDI), drug loading (DL), encapsulation efficiency (EE), and in vitro release as well as in vitro permeation. The concentration of MDZ in the brain after the intranasal administration of MDZ-CSNPs (Cmax 423.41 ± 10.23 ng/mL, tmax 2 h, and area under the curve from 0 to 480 min (AUC0-480) of 1920.87 ng.min/mL) was found to be comparatively higher to that achieved following intravenous (IV) administration of MDZ s...
Topical photodynamic therapy (PDT) is a promising alternative for malignant skin diseases such as... more Topical photodynamic therapy (PDT) is a promising alternative for malignant skin diseases such as basal cell carcinoma (BCC), due to its simplicity, enhanced patient compliance and localization of the residual photosensitivity to the site of application. However, insufficient photosensitizer penetration into the skin is the major issue of concern with topical PDT. Therefore, the aim of the present study was to enable penetration of photosensitizer to the different strata of the skin using a lipid nanocarrier system. We have attempted to develop a nanostructured lipid carrier (NLC) for the topical delivery of second generation photosensitizer, 5-amino levulinic acid (5-ALA), whose hydrophilicity and charge characteristic limit its percutaneous absorption. The microemulsion technique was used for preparing 5-ALA loaded NLC. The mean particle size, polydispersity index and entrapment efficiency of the optimized NLC of 5-ALA were found to be 185.2 ± 1.20, 0.156 ± 0.02 and 76.8 ± 2.58% r...
The aim of the present study was to improve bioavailability of an important antiretroviral drug, ... more The aim of the present study was to improve bioavailability of an important antiretroviral drug, Darunavir (DRV), which has low water solubility and poor intestinal absorption through solid dispersion (SD) approach incorporating polymer with P-glycoprotein inhibitory potential. A statistical approach where design of experiment (DoE) was used to prepare SD of DRV with incorporation of P-glycoprotein inhibitors. Using DoE, different methods of preparation, like melt, solvent evaporation, and spray drying method, utilizing carriers like Kolliphor TPGS and Soluplus were evaluated. The optimized SD was characterized by DSC, FTIR, XRD, and SEM and further evaluated for enhancement in absorption using everted gut sac model, effect of food on absorption of DRV, and in vivo prospect. DSC, FTIR, XRD, and SEM confirmed the amorphicity of drug in SD. Oral bioavailability studies revealed better absorption of DRV when given with food. Absorption studies and in vivo study findings demonstrated gr...
Hypertension, a worldwide epidemic at present, is not a disease in itself rather it is an importa... more Hypertension, a worldwide epidemic at present, is not a disease in itself rather it is an important risk factor for serious cardiovascular disorders including myocardial infarction, stroke, heart failure, and peripheral artery disease. Though numerous drugs acting via different mechanism of action are available in the market as conventional formulations for the treatment of hypertension but they face substantial challenges regarding their bioavailability, dosing and associated adverse effects which greatly limit their therapeutic efficacies. Various studies have demonstrated that nanocarriers can significantly increase the drug bioavailability thereby reducing the frequency of dosing in addition to minimizing toxicity associated with high dose of the drug. The present review provides an insight into the challenges associated with the conventional antihypertensive formulations and need for oral nanoparticulate systems in order to overcome problems associated with conventional formula...
Tacrolimus (TL), which is currently the mainstay of immunosuppressive therapy faces significant h... more Tacrolimus (TL), which is currently the mainstay of immunosuppressive therapy faces significant hurdles subsequent to its oral administration attributable to its poor aqueous solubility and extensive intestinal and hepatic first pass metabolism. Therefore, the present study aimed to design the stable nanostructured lipid carrier (NLC) of TL that would be able to overcome such hurdles. Capmul MCMC8 and Compritol 888ATO in 3:2 were selected as binary lipid phase on the basis of solubility study. An exhaustive screening of surfactants is done by aqueous titration to select the surfactant with best emulsifying potential and to optimize the concentration of lipids and surfactants in NLC. Different methods of preparation were explored and compared to optimize NLC which could have the best characteristic properties. TL-NLC was characterized for particle size, drug entrapment efficiency, crystal state, surface morphology and drug release. The obtained particle size, PDI and % drug entrapment efficiency of optimized formulations i.e., NLC-C2 and NLC-N2 were 70 ± 5.42 nm, 98 ± 7.52 nm; 0.43 ± 0.081, 0.2 ± 0.029 and 87 ± 2.34%, 94 ± 3.18%, respectively. The results of in vitro release studies showed significantly increased ( *** p < 0.001) and sustained release of TL from NLC dispersions as compared to drug suspension (95.73% from NLC-C2, 99.86% from NLC-N2 and 9.27% drug suspension in pH 1.2 in 24 h; 93.11% from NLC-C2, 96.65% from NLC-N2 and 10.2% drug suspension in pH 6.8 in 24 h). The study demonstrated that proper selection of excipients (by aqueous titration) and modification of method of preparation (by inclusion of cold step) would lead to production of NLC with best characteristic properties.
In the present study, midazolam (MDZ)-loaded chitosan nanoparticle formulation was investigated f... more In the present study, midazolam (MDZ)-loaded chitosan nanoparticle formulation was investigated for enhanced transport to the brain through the intranasal (IN) route. These days, IN MDZ is very much in demand for treating life-threatening seizure emergencies; therefore, its nanoparticle formulation was formulated in the present work because it could substantially improve its brain targeting via the IN route. MDZ-loaded chitosan nanoparticles (MDZ-CSNPs) were formulated and optimized by the ionic gelation method and then evaluated for particle size, particle size distribution (PDI), drug loading (DL), encapsulation efficiency (EE), and in vitro release as well as in vitro permeation. The concentration of MDZ in the brain after the intranasal administration of MDZ-CSNPs (Cmax 423.41 ± 10.23 ng/mL, tmax 2 h, and area under the curve from 0 to 480 min (AUC0-480) of 1920.87 ng.min/mL) was found to be comparatively higher to that achieved following intravenous (IV) administration of MDZ s...
Topical photodynamic therapy (PDT) is a promising alternative for malignant skin diseases such as... more Topical photodynamic therapy (PDT) is a promising alternative for malignant skin diseases such as basal cell carcinoma (BCC), due to its simplicity, enhanced patient compliance and localization of the residual photosensitivity to the site of application. However, insufficient photosensitizer penetration into the skin is the major issue of concern with topical PDT. Therefore, the aim of the present study was to enable penetration of photosensitizer to the different strata of the skin using a lipid nanocarrier system. We have attempted to develop a nanostructured lipid carrier (NLC) for the topical delivery of second generation photosensitizer, 5-amino levulinic acid (5-ALA), whose hydrophilicity and charge characteristic limit its percutaneous absorption. The microemulsion technique was used for preparing 5-ALA loaded NLC. The mean particle size, polydispersity index and entrapment efficiency of the optimized NLC of 5-ALA were found to be 185.2 ± 1.20, 0.156 ± 0.02 and 76.8 ± 2.58% r...
The aim of the present study was to improve bioavailability of an important antiretroviral drug, ... more The aim of the present study was to improve bioavailability of an important antiretroviral drug, Darunavir (DRV), which has low water solubility and poor intestinal absorption through solid dispersion (SD) approach incorporating polymer with P-glycoprotein inhibitory potential. A statistical approach where design of experiment (DoE) was used to prepare SD of DRV with incorporation of P-glycoprotein inhibitors. Using DoE, different methods of preparation, like melt, solvent evaporation, and spray drying method, utilizing carriers like Kolliphor TPGS and Soluplus were evaluated. The optimized SD was characterized by DSC, FTIR, XRD, and SEM and further evaluated for enhancement in absorption using everted gut sac model, effect of food on absorption of DRV, and in vivo prospect. DSC, FTIR, XRD, and SEM confirmed the amorphicity of drug in SD. Oral bioavailability studies revealed better absorption of DRV when given with food. Absorption studies and in vivo study findings demonstrated gr...
Hypertension, a worldwide epidemic at present, is not a disease in itself rather it is an importa... more Hypertension, a worldwide epidemic at present, is not a disease in itself rather it is an important risk factor for serious cardiovascular disorders including myocardial infarction, stroke, heart failure, and peripheral artery disease. Though numerous drugs acting via different mechanism of action are available in the market as conventional formulations for the treatment of hypertension but they face substantial challenges regarding their bioavailability, dosing and associated adverse effects which greatly limit their therapeutic efficacies. Various studies have demonstrated that nanocarriers can significantly increase the drug bioavailability thereby reducing the frequency of dosing in addition to minimizing toxicity associated with high dose of the drug. The present review provides an insight into the challenges associated with the conventional antihypertensive formulations and need for oral nanoparticulate systems in order to overcome problems associated with conventional formula...
Tacrolimus (TL), which is currently the mainstay of immunosuppressive therapy faces significant h... more Tacrolimus (TL), which is currently the mainstay of immunosuppressive therapy faces significant hurdles subsequent to its oral administration attributable to its poor aqueous solubility and extensive intestinal and hepatic first pass metabolism. Therefore, the present study aimed to design the stable nanostructured lipid carrier (NLC) of TL that would be able to overcome such hurdles. Capmul MCMC8 and Compritol 888ATO in 3:2 were selected as binary lipid phase on the basis of solubility study. An exhaustive screening of surfactants is done by aqueous titration to select the surfactant with best emulsifying potential and to optimize the concentration of lipids and surfactants in NLC. Different methods of preparation were explored and compared to optimize NLC which could have the best characteristic properties. TL-NLC was characterized for particle size, drug entrapment efficiency, crystal state, surface morphology and drug release. The obtained particle size, PDI and % drug entrapment efficiency of optimized formulations i.e., NLC-C2 and NLC-N2 were 70 ± 5.42 nm, 98 ± 7.52 nm; 0.43 ± 0.081, 0.2 ± 0.029 and 87 ± 2.34%, 94 ± 3.18%, respectively. The results of in vitro release studies showed significantly increased ( *** p < 0.001) and sustained release of TL from NLC dispersions as compared to drug suspension (95.73% from NLC-C2, 99.86% from NLC-N2 and 9.27% drug suspension in pH 1.2 in 24 h; 93.11% from NLC-C2, 96.65% from NLC-N2 and 10.2% drug suspension in pH 6.8 in 24 h). The study demonstrated that proper selection of excipients (by aqueous titration) and modification of method of preparation (by inclusion of cold step) would lead to production of NLC with best characteristic properties.
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Papers by Saba Khan