Papers by Waleed M Khattab
Journal of Pharmaceutical Innovation, 2020
Purpose This study aims to design oily-core nanocapsules for poorly water-soluble antihypertensiv... more Purpose This study aims to design oily-core nanocapsules for poorly water-soluble antihypertensive drug olmesartan medoxomil (OM) and optimize systematically the in-vitro characteristics of prepared nanosystems. The study represents an organized methodology for screening and studying significant parameters affecting polymeric nanocapsule formulation and characterization. Method A full two-level (2 3) factorial design was conducted to optimize the characteristics of poly-Ɛ-caprolactone oily-core nanocapsules (ONC) which were prepared using interfacial deposition of preformed polymer technique. The selected independent variables were the concentration of polymer, aqueous/organic phase ratio, and magnetic stirring rate. Results The selected formulation and processing variables significantly affected the tested responses. The developed ONC formulae showed a particle size (PS) range from 180.63 ± 0.31 to 338.93 ± 0.42 nm, polydispersity index values (PDI) were < 0.5, negative zeta potential (ZP) values from 20.17 ± 0.21 to 32.83 ± 0.21 mV, and entrapment efficiency (EE) values range from 74.63 ± 0.15 to 93.37 ± 0.15%. In-vitro drug release testing showed a controlled release pattern for OM over 8 h following Hixson-Crowell model for the optimized formula. Transmission electron micrographs (TEM) showed a perfect spherical nanocapsule with a clear polymeric coat. Stability study for 3 months at refrigerated and room temperatures showed non-significant variations and excellent stability for the prepared colloidal nanocapsular dispersion in terms of particle size (PS), zeta potential (ZP), polydispersity index (PDI), and entrapment efficiency (EE). Conclusion It is concluded that ONC are such a promising nanosystem which can significantly improve the biopharmaceutical behavior of OM.
Zolmitriptan is a serotonin (5-HT1) receptor agonist used for the treatment of migraine with or w... more Zolmitriptan is a serotonin (5-HT1) receptor agonist used for the treatment of migraine with or without aura. Its half-life is 2.5 to 3 hrs and it undergoes hepatic first pass metabolism. Absolute oral bioavailability is about 40 %. In order to improve the bioavailability and efficacy, buccal mucoadhesive tablets of Zolmitriptan were prepared using different mucoadhesive polymers (natural and synthetic) in different ratios by direct compression technique. Buccal tablets were evaluated for a number of parameters such as: hardness, thickness, diameter, friability, weight uniformity, drug content uniformity, surface pH, ex-vivo residence time, in-vitro swelling study, in-vitro mucoadhesive strength and in-vitro drug release study. Pre-formulation studies such as drug- excipients compatibility study using IR and DSC and micromeritics study were also done. All prepared tablets had smooth surface and elegant appearance. Tablets were weighing 150-156 mg, hardness was 6-8 kg/cm2 , thickness...
Drug Development and Industrial Pharmacy, 2020
Abstract Objective: This study aims to detect the enhancement in the oral bioavailability of a po... more Abstract Objective: This study aims to detect the enhancement in the oral bioavailability of a poorly water-soluble antihypertensive drug Olmesartan Medoxomil (OM) due to the formulation of lyophilized oily-core nanocapsules. Significance: A comparative pharmacokinetic study in rats was conducted for oily-core polymeric nanocapsules (ONC) after formulation and lyophilization against market tablet products to show the significant improvement in oral absorption of OM. Materials and methods: OM loaded ONC were prepared using poly-Ɛ-caprolactone (0.5% w/v) as a polymer and an oily core of Labrafac PG® by applying a well-controlled nanoprecipitation technique in terms of injection rate (80 mL/h) and magnetic stirring rate (300 rpm). The prepared lyophilized ONC were in-vitro characterized after reconstitution and evaluated in-vivo for oral bioavailability after a single OM oral dose (20 mg/kg) of reconstituted lyophilized ONC dispersion was administered to rats. Results: The prepared lyophilized ONC containing 10% w/v mannitol showed an average particle size of 158 nm, polydispersity index of 0.37, negative zeta potential value equals 33.9 and entrapment efficiency of 90%. The dissolution profile for OM from lyophilized ONC powder filled into hard gelatin capsules (HGC) showed a 1.8-fold increase in dissolution rate as compared to the pure drug. In-vivo pharmacokinetic study in rats revealed a significant enhancement in the oral bioavailability of OM with 1.6-fold increase for AUC0-24 and a 1.9-fold increase for Cmax as compared to marketed product. Conclusion: It is concluded that the formulation of lyophilized ONC for OM can significantly enhance its oral bioavailability and consequently, its therapeutic efficacy and patient compliance.
Mucoadhesion was employed for improving performance and bioavailability of many drugs. Different ... more Mucoadhesion was employed for improving performance and bioavailability of many drugs. Different dosage forms were developed based on this principle. This study aims to prepare bucco-adhesive tablets of anti-migraine drug zolmitriptan as a suitable candidate for improving its oral bioavailability and therapeutic efficacy and to evaluate them for many pre/post-formulation parameters in-vitro/ex-vivo. The bucco-adhesive tablets containing 2.5 mg zolmitriptan were prepared using carbopol 934LR as a primary polymer alone or in combination with chitosan or xanthan gum as secondary polymers by direct compression. Drug-excipients compatibility and micromeritics study were carried out. Tablets were evaluated for physico-chemical parameters, surface pH, ex-vivo residence time, in-vitro swelling study, ex-vivo mucoadhesive strength, in-vitro drug release study, ex-vivo permeation study and physical stability in human saliva. No interactions were found between drug and excipients. Tablets had ...
Journal of Pharmaceutical Innovation, 2020
Purpose
This study aims to design oily-core nanocapsules for poorly water-soluble antihypertensiv... more Purpose
This study aims to design oily-core nanocapsules for poorly water-soluble antihypertensive drug olmesartan medoxomil (OM) and optimize systematically the in-vitro characteristics of prepared nanosystems. The study represents an organized methodology for screening and studying significant parameters affecting polymeric nanocapsule formulation and characterization.
Method
A full two-level (23) factorial design was conducted to optimize the characteristics of poly-Ɛ-caprolactone oily-core nanocapsules (ONC) which were prepared using interfacial deposition of preformed polymer technique. The selected independent variables were the concentration of polymer, aqueous/organic phase ratio, and magnetic stirring rate.
Results
The selected formulation and processing variables significantly affected the tested responses. The developed ONC formulae showed a particle size (PS) range from 180.63 ± 0.31 to 338.93 ± 0.42 nm, polydispersity index values (PDI) were < 0.5, negative zeta potential (ZP) values from 20.17 ± 0.21 to 32.83 ± 0.21 mV, and entrapment efficiency (EE) values range from 74.63 ± 0.15 to 93.37 ± 0.15%. In-vitro drug release testing showed a controlled release pattern for OM over 8 h following Hixson-Crowell model for the optimized formula. Transmission electron micrographs (TEM) showed a perfect spherical nanocapsule with a clear polymeric coat. Stability study for 3 months at refrigerated and room temperatures showed non-significant variations and excellent stability for the prepared colloidal nanocapsular dispersion in terms of particle size (PS), zeta potential (ZP), polydispersity index (PDI), and entrapment efficiency (EE).
Conclusion
It is concluded that ONC are such a promising nanosystem which can significantly improve the biopharmaceutical behavior of OM.
Drug Development and Industrial Pharmacy, 2020
Objective: This study aims to detect the enhancement in oral bioavailability of a poorly water-so... more Objective: This study aims to detect the enhancement in oral bioavailability of a poorly water-soluble antihypertensive drug Olmesartan Medoxomil (OM) due to formulation of lyophilized oily-core nanocapsules.
Significance: A comparative pharmacokinetics study in rats was conducted for oily-core polymeric nanocapsules (ONC) after formulation and lyophilization against market tablet product to show the significant improvement in oral absorption of OM.
Materials and methods: OM loaded ONC were prepared using poly-Ɛ-caprolactone (0.5% w/v) as a polymer and an oily core of Labrafac PG® by applying a well-controlled nanoprecipitation technique in terms of injection rate (80 mL/h) and magnetic stirring rate (300 rpm). The prepared lyophilized ONC were in-vitro characterized after reconstitution and evaluated in-vivo for oral bioavailability after a single OM oral dose (20 mg/kg) of reconstituted lyophilized ONC dispersion was administered to rats.
Results: The prepared lyophilized ONC containing 10% w/v mannitol showed an average particle size of 158 nm, polydispersity index of 0.37, negative zetapotential value equals 33.9 and entrapment efficiency of 90%. Dissolution profile for OM from lyophilized ONC powder filled into hard gelatin capsules (HGC) showed 1.8-fold increase in dissolution rate as compared to the pure drug. In-vivo pharmacokinetics study in rats revealed a significant enhancement in oral bioavailability of OM with 1.6-fold increase for AUC0-24 and 1.9-fold increase for Cmax as compared to marketed product.
Conclusion: It is concluded that formulation of lyophilized ONC for OM can significantly enhance its oral bioavailability and consequently, its therapeutic efficacy and patient compliance.
Losartan potassium is a water soluble drug, belongs to Biopharmaceutics Classification System (BC... more Losartan potassium is a water soluble drug, belongs to Biopharmaceutics Classification System (BCS) class III drugs with a short half life and an extensive hepatic first pass metabolism. Buccal route was employed to deliver several drugs to the systemic circulation through the internal jugular vein bypassing the extensive pre-systemic metabolism in liver. Simple sustained release mucoadhesive system for such drugs was developed in the form of buccal tablets due to high compliance among other dosage forms. The prepared mucoadhesive tablets were containing 25 mg of losartan potassium and carbopol 934LR as a primary polymer with or without secondary polymers and prepared by direct compression. Drug-excipients compatibility studies were carried out along with micromeritics study prior to compression. Buccal tablets were then evaluated for in vitro and ex vivo performance. Optimum formula was selected based on a ranking methodology and then, it was subjected to ex vivo permeation and phy...
Zolmitriptan is a serotonin (5 treatment of migraine with or without aura. Its half it undergoes ... more Zolmitriptan is a serotonin (5 treatment of migraine with or without aura. Its half it undergoes hepatic first pass metabolism. Absolute oral bi about 40 %. In order to improve the bioavailability and efficacy, buccal mucoadhesive tablets of Zolmitriptan were prepared using different mucoadhesive polymers (natural and synthetic) in different ratios by direct compression technique. of parameters such as: hardness, thickness, diameter, friability, weight uniformity, drug content uniformity, surface pH, ex in-vitro swelling study, in release study. Pre compatibility study using IR and DSC and micromeritics study were also done. All prepared tablets had smooth surface and elegant appearance. Tablets were weighing 150 was 3.2 were within pharmacopeial limits. All tablets showed moderate swelling and biocompatibility with buccal mucous membrane. Ex time was not less than strength. In drug was released within 7 hrs. Release of Zolmitriptan from all tablets followed zero order kinetics. Hence, these formulations of are promising ones as a controlled drug delivery system that will lead to improved bioavailability and greater therapeutic efficacy.
British Journal of Pharmaceutical Research, 2014
Objective: This study aims to develop controlled release buccal tablets of losartan potassium bas... more Objective: This study aims to develop controlled release buccal tablets of losartan potassium based on bioadhesion using direct compression technique. Materials and Methods: The bioadhesive buccal tablets of losartan potassium were prepared after preliminary drug-excipients compatibility studies and micromeretics study for powder blends. The tablets were prepared by direct compression utilizing carbopol 934LR as a primary bioadhesive polymer either with or without chitosan or hydroxypropyl methylcellulose E15LV as secondary polymers. Other excipients included PVP K30 as a binder, magnesium stearate as a lubricant and mannitol as a diluent. The tablets were evaluated for weight variation, thickness and diameter, hardness, friability, drug content, surface pH, Ex-vivo residence time and bioadhesion force, In-vitro swelling and drug release study. The analysis of the release profiles in the light of distinct kinetic models (zero order, first order, Higuchi, Hixson-Crowell and Korsmeyer-Peppas) was carried out. Results and Discussion: The formula containing 40% w/w bioadhesive polymers of carbopol 934LR and chitosan (1:2) was selected as the optimum one based on a ranking 1175 methodology and then, it was subjected to Ex-vivo permeation and physical stability study in human saliva. Swelling index was 78.32±1.84% after 7h and tablets showed a neutral surface pH. Ex-vivo residence time was long enough for more than 10h. Ex-vivo bioadhesion force was 0.38±0.01N. Drug release was 57.64±3.43% after 8h following zero order kinetics with a steady state permeation flux of 0.959mg/cm 2 h. Tablets were physically stable in human saliva. Conclusion: These formulae improved, controlled and prolonged the release of losartan potassium from a buccal bioadhesive system for at least 8h in a simple way which can achieve a high patient compliance.
Mucoadhesion was employed for improving performance and bioavailability of many drugs. Different ... more Mucoadhesion was employed for improving performance and bioavailability of many drugs. Different dosage forms were developed based on this principle. This study aims to prepare bucco-adhesive tablets of anti-migraine drug zolmitriptan as a suitable candidate for improving its oral bioavailability and therapeutic efficacy and to evaluate them for many pre/post-formulation parameters in-vitro/exvivo. The bucco-adhesive tablets containing 2.5 mg zolmitriptan were prepared using carbopol 934LR as a primary polymer alone or in combination with chitosan or xanthan gum as secondary polymers by direct compression. Drug-excipients compatibility and micromeritics study were carried out. Tablets were evaluated for physico-chemical parameters, surface pH, ex-vivo residence time, in-vitro swelling study, ex-vivo mucoadhesive strength, in-vitro drug release study, ex-vivo permeation study and physical stability in human saliva. No interactions were found between drug and excipients. Tablets had good physico-chemical characters. Formulation containing carbopol 934LR and chitosan in a ratio of 1: 3 approximately was the optimum one. It swelled by only 37.67±0.65% after 5 h and showed a nearly neutral surface pH. Ex-vivo residence time was long enough for delivery of the drug for more than 8 h. Ex-vivo mucoadhesive strength was 32.7±2.1 g. Drug release was 86.93±3.73 % after 7 h following zero order kinetics and permeation flux was 0.045 mg/cm 2 h. Tablets were physically stable W WO OR RL LD D J JO OU UR RN NA AL L O OF F P PH HA AR RM MA AC CY Y A AN ND D P PH HA AR RM MA AC CE EU UT TI IC CA AL L S SC CI IE EN NC CE ES S V Vo ol lu um me e 2 2, , I Is ss su ue e 6 6, , 4 42 22 25 5--4 42 24 48 8. . R Re es se ea ar rc ch h A Ar rt ti ic cl le e I
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Papers by Waleed M Khattab
This study aims to design oily-core nanocapsules for poorly water-soluble antihypertensive drug olmesartan medoxomil (OM) and optimize systematically the in-vitro characteristics of prepared nanosystems. The study represents an organized methodology for screening and studying significant parameters affecting polymeric nanocapsule formulation and characterization.
Method
A full two-level (23) factorial design was conducted to optimize the characteristics of poly-Ɛ-caprolactone oily-core nanocapsules (ONC) which were prepared using interfacial deposition of preformed polymer technique. The selected independent variables were the concentration of polymer, aqueous/organic phase ratio, and magnetic stirring rate.
Results
The selected formulation and processing variables significantly affected the tested responses. The developed ONC formulae showed a particle size (PS) range from 180.63 ± 0.31 to 338.93 ± 0.42 nm, polydispersity index values (PDI) were < 0.5, negative zeta potential (ZP) values from 20.17 ± 0.21 to 32.83 ± 0.21 mV, and entrapment efficiency (EE) values range from 74.63 ± 0.15 to 93.37 ± 0.15%. In-vitro drug release testing showed a controlled release pattern for OM over 8 h following Hixson-Crowell model for the optimized formula. Transmission electron micrographs (TEM) showed a perfect spherical nanocapsule with a clear polymeric coat. Stability study for 3 months at refrigerated and room temperatures showed non-significant variations and excellent stability for the prepared colloidal nanocapsular dispersion in terms of particle size (PS), zeta potential (ZP), polydispersity index (PDI), and entrapment efficiency (EE).
Conclusion
It is concluded that ONC are such a promising nanosystem which can significantly improve the biopharmaceutical behavior of OM.
Significance: A comparative pharmacokinetics study in rats was conducted for oily-core polymeric nanocapsules (ONC) after formulation and lyophilization against market tablet product to show the significant improvement in oral absorption of OM.
Materials and methods: OM loaded ONC were prepared using poly-Ɛ-caprolactone (0.5% w/v) as a polymer and an oily core of Labrafac PG® by applying a well-controlled nanoprecipitation technique in terms of injection rate (80 mL/h) and magnetic stirring rate (300 rpm). The prepared lyophilized ONC were in-vitro characterized after reconstitution and evaluated in-vivo for oral bioavailability after a single OM oral dose (20 mg/kg) of reconstituted lyophilized ONC dispersion was administered to rats.
Results: The prepared lyophilized ONC containing 10% w/v mannitol showed an average particle size of 158 nm, polydispersity index of 0.37, negative zetapotential value equals 33.9 and entrapment efficiency of 90%. Dissolution profile for OM from lyophilized ONC powder filled into hard gelatin capsules (HGC) showed 1.8-fold increase in dissolution rate as compared to the pure drug. In-vivo pharmacokinetics study in rats revealed a significant enhancement in oral bioavailability of OM with 1.6-fold increase for AUC0-24 and 1.9-fold increase for Cmax as compared to marketed product.
Conclusion: It is concluded that formulation of lyophilized ONC for OM can significantly enhance its oral bioavailability and consequently, its therapeutic efficacy and patient compliance.
This study aims to design oily-core nanocapsules for poorly water-soluble antihypertensive drug olmesartan medoxomil (OM) and optimize systematically the in-vitro characteristics of prepared nanosystems. The study represents an organized methodology for screening and studying significant parameters affecting polymeric nanocapsule formulation and characterization.
Method
A full two-level (23) factorial design was conducted to optimize the characteristics of poly-Ɛ-caprolactone oily-core nanocapsules (ONC) which were prepared using interfacial deposition of preformed polymer technique. The selected independent variables were the concentration of polymer, aqueous/organic phase ratio, and magnetic stirring rate.
Results
The selected formulation and processing variables significantly affected the tested responses. The developed ONC formulae showed a particle size (PS) range from 180.63 ± 0.31 to 338.93 ± 0.42 nm, polydispersity index values (PDI) were < 0.5, negative zeta potential (ZP) values from 20.17 ± 0.21 to 32.83 ± 0.21 mV, and entrapment efficiency (EE) values range from 74.63 ± 0.15 to 93.37 ± 0.15%. In-vitro drug release testing showed a controlled release pattern for OM over 8 h following Hixson-Crowell model for the optimized formula. Transmission electron micrographs (TEM) showed a perfect spherical nanocapsule with a clear polymeric coat. Stability study for 3 months at refrigerated and room temperatures showed non-significant variations and excellent stability for the prepared colloidal nanocapsular dispersion in terms of particle size (PS), zeta potential (ZP), polydispersity index (PDI), and entrapment efficiency (EE).
Conclusion
It is concluded that ONC are such a promising nanosystem which can significantly improve the biopharmaceutical behavior of OM.
Significance: A comparative pharmacokinetics study in rats was conducted for oily-core polymeric nanocapsules (ONC) after formulation and lyophilization against market tablet product to show the significant improvement in oral absorption of OM.
Materials and methods: OM loaded ONC were prepared using poly-Ɛ-caprolactone (0.5% w/v) as a polymer and an oily core of Labrafac PG® by applying a well-controlled nanoprecipitation technique in terms of injection rate (80 mL/h) and magnetic stirring rate (300 rpm). The prepared lyophilized ONC were in-vitro characterized after reconstitution and evaluated in-vivo for oral bioavailability after a single OM oral dose (20 mg/kg) of reconstituted lyophilized ONC dispersion was administered to rats.
Results: The prepared lyophilized ONC containing 10% w/v mannitol showed an average particle size of 158 nm, polydispersity index of 0.37, negative zetapotential value equals 33.9 and entrapment efficiency of 90%. Dissolution profile for OM from lyophilized ONC powder filled into hard gelatin capsules (HGC) showed 1.8-fold increase in dissolution rate as compared to the pure drug. In-vivo pharmacokinetics study in rats revealed a significant enhancement in oral bioavailability of OM with 1.6-fold increase for AUC0-24 and 1.9-fold increase for Cmax as compared to marketed product.
Conclusion: It is concluded that formulation of lyophilized ONC for OM can significantly enhance its oral bioavailability and consequently, its therapeutic efficacy and patient compliance.