European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, Jan 12, 2017
Dutasteride, used for treating benign prostate hyperplasia (BPH), promotes hair growth. To enhanc... more Dutasteride, used for treating benign prostate hyperplasia (BPH), promotes hair growth. To enhance delivery to the hair follicles and reduce systemic effects, in this study dutasteride has been formulated for topical application, in a nanostructured lipid carrier (NLC) coated with chitosan oligomer-stearic acid (CSO-SA). CSO-SA has been successfully synthesized, as confirmed using (1)H NMR and FTIR. Formulation of dutasteride-loaded nanostructured lipid carriers (DST-NLCs) was optimised using 2(3) full factorial design. This formulation was coated with different concentrations of stearic acid-chitosan solution. Coating DST-NLCs with 5% SA-CSO increased mean size from 187.6 ± 7.0 nm to 220.1 ± 11.9 nm, and modified surface charge, with zeta potentials being -18.3 ± 0.9 mV and +25.8 ± 1.1 mV for uncoated and coated DST-NLCs respectively. Transmission electron microscopy showed all formulations comprised approximately spherical particles. DST-NLCs, coated and uncoated with CSO-SA, exhi...
Dutasteride, licensed as an oral medicine for the treatment of benign prostatic hypoplasia, has b... more Dutasteride, licensed as an oral medicine for the treatment of benign prostatic hypoplasia, has been investigated as a treatment for androgenic alopecia. In this study, the potential for dustasteride to be delivered topically in order to reduce systemic exposure, irritation of the skin, and also cytotoxicity was explored. Chitosan oligomer (CSO) was successfully synthesised with lauric acid as a coating for a dutasteride-loaded nanostructured lipid carriers (DST-NLCs) system. DST-NLCs were prepared using a combination of melt-dispersion and ultrasonication. These negatively charged NLCs (−18.0 mV) had a mean particle size of ~184 nm, which was not significantly increased (p > 0.05) when coated with lauric acid-chitosan oligomer (CSO-LA), whilst the surface charge changed to positive (+24.8 mV). The entrapment efficiency of DST-NLCs was 97%, and coated and uncoated preparations were physically stable for up to 180 days at 4–8 °C. The drug release was slower from DST-NLCs coated wi...
Male pattern baldness (MPB) is a common condition that has a negative impact on the psycho-social... more Male pattern baldness (MPB) is a common condition that has a negative impact on the psycho-social health of many men. This study aims to engineer an alcohol-free formulation to cater for individuals who may have had allergic reactions to alcohol-based preparations. A lipid-based nanoparticle system composed of stearic and oleic acid (solid and liquid lipid) was used to deliver dutasteride (DST) for topical application. Two compositions, with oleic acid (Formulation A) and without (Formulation B), were compared to analyse the role of oleic acid as a potential active ingredient in addition to DST. DST-loaded LNP were prepared using the emulsification–ultrasonication method. All of the prepared formulations were spherical in shape in the nanometric size range (150–300 nm), with entrapment efficiencies of >75%. X-ray diffractograms revealed that DST exists in an amorphous form within the NLP matrices. The drug release behaviour from both LNP preparations displayed slow release of DST...
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 2016
This study has investigated complexation of fisetin, a natural flavonoid, with three types of cyc... more This study has investigated complexation of fisetin, a natural flavonoid, with three types of cyclodextrins to improve its solubility. Sulfobutylether-β-cyclodextrin (SBE-β-CD) showed the highest complexation efficiency while maintaining the in vitro antioxidant activity of fisetin. Addition of 20%v/v ethanol in water improved the amount of solubilized fisetin in the complex 5.9-fold compared to the system containing water alone. Spray drying of fisetin-SBE-β-CD complex solution in the presence of ethanol produced a dry powder with improved aerosolization properties when delivered from a dry powder inhaler, indicated by a 2-fold increase in the fine particle fraction (FPF) compared to the powder produced from the complex solution containing water alone. The pitted morphological surface of these particles suggested a more hollow internal structure, indicating a lighter and less dense powder. Incorporation of 20%w/w leucine improved the particle size distribution of the powder and fur...
Dutasteride, used for treating benign prostate hyperplasia (BPH), promotes hair growth. To enhanc... more Dutasteride, used for treating benign prostate hyperplasia (BPH), promotes hair growth. To enhance delivery to the hair follicles and reduce systemic effects, in this study dutasteride has been formulated for topical application, in a nanostructured lipid carrier (NLC) coated with chitosan oligomer-stearic acid (CSO-SA). CSO-SA has been successfully synthesized, as confirmed using 1 H NMR and FTIR. Formulation of dutasteride-loaded nanostructured lipid carriers (DST-NLCs) was optimized using a 2 3 full factorial design. This formulation was coated with different concentrations of stearic acid-chitosan solution. Coating DST-NLCs with 5% SA-CSO increased mean size from 187.6 ± 7.0 nm to 220.1 ± 11.9 nm, and modified surface charge, with zeta potentials being À18.3 ± 0.9 mV and +25.8 ± 1.1 mV for uncoated and coated DST-NLCs respectively. Transmission electron microscopy showed all formulations comprised approximately spherical particles. DST-NLCs, coated and uncoated with CSO-SA, exhibited particle size stability over 60 days, when stored at 4–8 °C. However, NLCs coated with CSO (without conjugation) showed aggregation when stored at 4–8 °C after 30 days. The measured particle size for all formulations stored at 25 °C suggested aggregation, which was greatest for DST-NLCs coated with 10% CSO-SA and 5% CSO. All nanoparticle formulations exhibited rapid release in an in vitro release study, with uncoated NLCs exhibiting the fastest release rate. Using a Franz diffusion cell, no dutasteride permeated through pig ear skin after 48 h, such that it was not detected in the receptor chamber for all samples. The amount of dutasteride in the skin was significantly different (p < 0.05) for DST-NLCs (6.09 ± 1.09 lg/cm 2) without coating and those coated with 5% CSO-SA (2.82 ± 0.40 lg/cm 2), 10% CSO-SA (2.70 ± 0.35 lg/cm 2) and CSO (2.11 ± 0.64 lg/cm 2). There was a significant difference (p < 0.05) in the cytotoxicity (IC 50) between dutasteride alone and in the nanoparticles. DST-NLCs coated and uncoated with CSO-SA increased the maximum non-toxic concentration by 20-fold compared to dutasteride alone. These studies indicate that a stearic acid-chitosan conjugate was successfully prepared, and modified the surface charge of DST-NLCs from negative to positive. These stable, less cytotoxic, positively-charged dutasteride-loaded nanostruc-tured lipid carriers, with stearic acid-chitosan oligomer conjugate, are appropriate for topical delivery and have potential for promotion of hair growth.
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, Jan 12, 2017
Dutasteride, used for treating benign prostate hyperplasia (BPH), promotes hair growth. To enhanc... more Dutasteride, used for treating benign prostate hyperplasia (BPH), promotes hair growth. To enhance delivery to the hair follicles and reduce systemic effects, in this study dutasteride has been formulated for topical application, in a nanostructured lipid carrier (NLC) coated with chitosan oligomer-stearic acid (CSO-SA). CSO-SA has been successfully synthesized, as confirmed using (1)H NMR and FTIR. Formulation of dutasteride-loaded nanostructured lipid carriers (DST-NLCs) was optimised using 2(3) full factorial design. This formulation was coated with different concentrations of stearic acid-chitosan solution. Coating DST-NLCs with 5% SA-CSO increased mean size from 187.6 ± 7.0 nm to 220.1 ± 11.9 nm, and modified surface charge, with zeta potentials being -18.3 ± 0.9 mV and +25.8 ± 1.1 mV for uncoated and coated DST-NLCs respectively. Transmission electron microscopy showed all formulations comprised approximately spherical particles. DST-NLCs, coated and uncoated with CSO-SA, exhi...
Dutasteride, licensed as an oral medicine for the treatment of benign prostatic hypoplasia, has b... more Dutasteride, licensed as an oral medicine for the treatment of benign prostatic hypoplasia, has been investigated as a treatment for androgenic alopecia. In this study, the potential for dustasteride to be delivered topically in order to reduce systemic exposure, irritation of the skin, and also cytotoxicity was explored. Chitosan oligomer (CSO) was successfully synthesised with lauric acid as a coating for a dutasteride-loaded nanostructured lipid carriers (DST-NLCs) system. DST-NLCs were prepared using a combination of melt-dispersion and ultrasonication. These negatively charged NLCs (−18.0 mV) had a mean particle size of ~184 nm, which was not significantly increased (p > 0.05) when coated with lauric acid-chitosan oligomer (CSO-LA), whilst the surface charge changed to positive (+24.8 mV). The entrapment efficiency of DST-NLCs was 97%, and coated and uncoated preparations were physically stable for up to 180 days at 4–8 °C. The drug release was slower from DST-NLCs coated wi...
Male pattern baldness (MPB) is a common condition that has a negative impact on the psycho-social... more Male pattern baldness (MPB) is a common condition that has a negative impact on the psycho-social health of many men. This study aims to engineer an alcohol-free formulation to cater for individuals who may have had allergic reactions to alcohol-based preparations. A lipid-based nanoparticle system composed of stearic and oleic acid (solid and liquid lipid) was used to deliver dutasteride (DST) for topical application. Two compositions, with oleic acid (Formulation A) and without (Formulation B), were compared to analyse the role of oleic acid as a potential active ingredient in addition to DST. DST-loaded LNP were prepared using the emulsification–ultrasonication method. All of the prepared formulations were spherical in shape in the nanometric size range (150–300 nm), with entrapment efficiencies of >75%. X-ray diffractograms revealed that DST exists in an amorphous form within the NLP matrices. The drug release behaviour from both LNP preparations displayed slow release of DST...
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 2016
This study has investigated complexation of fisetin, a natural flavonoid, with three types of cyc... more This study has investigated complexation of fisetin, a natural flavonoid, with three types of cyclodextrins to improve its solubility. Sulfobutylether-β-cyclodextrin (SBE-β-CD) showed the highest complexation efficiency while maintaining the in vitro antioxidant activity of fisetin. Addition of 20%v/v ethanol in water improved the amount of solubilized fisetin in the complex 5.9-fold compared to the system containing water alone. Spray drying of fisetin-SBE-β-CD complex solution in the presence of ethanol produced a dry powder with improved aerosolization properties when delivered from a dry powder inhaler, indicated by a 2-fold increase in the fine particle fraction (FPF) compared to the powder produced from the complex solution containing water alone. The pitted morphological surface of these particles suggested a more hollow internal structure, indicating a lighter and less dense powder. Incorporation of 20%w/w leucine improved the particle size distribution of the powder and fur...
Dutasteride, used for treating benign prostate hyperplasia (BPH), promotes hair growth. To enhanc... more Dutasteride, used for treating benign prostate hyperplasia (BPH), promotes hair growth. To enhance delivery to the hair follicles and reduce systemic effects, in this study dutasteride has been formulated for topical application, in a nanostructured lipid carrier (NLC) coated with chitosan oligomer-stearic acid (CSO-SA). CSO-SA has been successfully synthesized, as confirmed using 1 H NMR and FTIR. Formulation of dutasteride-loaded nanostructured lipid carriers (DST-NLCs) was optimized using a 2 3 full factorial design. This formulation was coated with different concentrations of stearic acid-chitosan solution. Coating DST-NLCs with 5% SA-CSO increased mean size from 187.6 ± 7.0 nm to 220.1 ± 11.9 nm, and modified surface charge, with zeta potentials being À18.3 ± 0.9 mV and +25.8 ± 1.1 mV for uncoated and coated DST-NLCs respectively. Transmission electron microscopy showed all formulations comprised approximately spherical particles. DST-NLCs, coated and uncoated with CSO-SA, exhibited particle size stability over 60 days, when stored at 4–8 °C. However, NLCs coated with CSO (without conjugation) showed aggregation when stored at 4–8 °C after 30 days. The measured particle size for all formulations stored at 25 °C suggested aggregation, which was greatest for DST-NLCs coated with 10% CSO-SA and 5% CSO. All nanoparticle formulations exhibited rapid release in an in vitro release study, with uncoated NLCs exhibiting the fastest release rate. Using a Franz diffusion cell, no dutasteride permeated through pig ear skin after 48 h, such that it was not detected in the receptor chamber for all samples. The amount of dutasteride in the skin was significantly different (p < 0.05) for DST-NLCs (6.09 ± 1.09 lg/cm 2) without coating and those coated with 5% CSO-SA (2.82 ± 0.40 lg/cm 2), 10% CSO-SA (2.70 ± 0.35 lg/cm 2) and CSO (2.11 ± 0.64 lg/cm 2). There was a significant difference (p < 0.05) in the cytotoxicity (IC 50) between dutasteride alone and in the nanoparticles. DST-NLCs coated and uncoated with CSO-SA increased the maximum non-toxic concentration by 20-fold compared to dutasteride alone. These studies indicate that a stearic acid-chitosan conjugate was successfully prepared, and modified the surface charge of DST-NLCs from negative to positive. These stable, less cytotoxic, positively-charged dutasteride-loaded nanostruc-tured lipid carriers, with stearic acid-chitosan oligomer conjugate, are appropriate for topical delivery and have potential for promotion of hair growth.
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Papers by Khalid Sheikh