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Papers by El-Sayed Khafagy

Research paper thumbnail of Drug Delivery from Microsponges: A Review Article

Records of Pharmaceutical and Biomedical Sciences

Microsponges are micro-porous particles, used mainly for topical and recently for oral administra... more Microsponges are micro-porous particles, used mainly for topical and recently for oral administration. Microsponges have many advantages which make it a versatile drug delivery system. Microsponges can suspended or entrap a wide variety of substances and then be incorporated into a formulated product such as a gel, cream, liquid, or powder. Moreover, they may enhance stability, reduce side effects and modify drug release related to its porous structure which allows the active ingredient to sustain over time. The aim of this article is to provide details about microsponges including the method of preparation, characterization, mechanism of drug release from microsponges, different formulation and process factors, and a few applications about microsponges which are either proven or under research.

Research paper thumbnail of Atorvastatin-loaded pro-nanolipospheres with ameliorated oral bioavailability and antidyslipidemic activity

Colloids and Surfaces B: Biointerfaces

Despite significant advances in oral drug delivery technologies, many drugs are prone to limited ... more Despite significant advances in oral drug delivery technologies, many drugs are prone to limited oral bioavailability due to biological barriers that hinder drug absorption. Pro-nanolipospheres (PNL) are a form of delivery system that can potentiate the oral bioavailability of poorly water-soluble drugs through a variety of processes, including increased drug solubility and protecting them from degradation by intestinal or hepatic first-pass metabolism. In this study, pro-nanolipospheres were employed as a delivery vehicle for improving the oral bioavailability of the lipophilic statin, atorvastatin (ATR). Various ATR-loaded PNL formulations, composed of various pharmaceutical ingredients, were prepared by the pre-concentrate method and characterized by determining particle size, surface charge, and encapsulation efficiency. An optimized formula (ATR-PT PNL) showing the smallest particle size, highest zeta potential, and highest encapsulation efficiency was selected for further in vivo investigations. The in vivo pharmacodynamic experiments demonstrated that the optimized ATR-PT PNL formulation exerted a potent hypolipidemic effect in a Poloxamer® 407-induced hyper-lipidaemia rat model by restoring normal cholesterol and triglyceride serum levels along with alleviating serum levels of LDL while elevating serum HDL levels, compared to pure drug suspensions and marketed ATR (Lipitor®). Most importantly, oral administration of the optimized ATR-PT PNL formulation showed a dramatic increase in ATR oral bioavailability, as evinced by a 1.7- and 3.6-fold rise in systemic bioavailability when compared with oral commercial ATR suspensions (Lipitor®) and pure drug suspension, respectively. Collectively, pro-nanolipospheres might represent a promising delivery vehicle for enhancing the oral bioavailability of poorly water-soluble drugs.

Research paper thumbnail of Lipospheres and Pro-Nanolipospheres: Advancements in Drug Delivery Systems

Records of Pharmaceutical and Biomedical Sciences

The usefulness of nanotechnology nowadays in improving the performance of different active pharma... more The usefulness of nanotechnology nowadays in improving the performance of different active pharmaceutical ingredients (API) has generated a great deal of excitement worldwide. These nano-systems offer the advantage of higher bioavailability, lower toxicity, and the ability to deliver drugs with low half-life or low permeability. Lipid nano-based carriers have been extensively used for their ability to protect the API from degradation and their safety as these used lipids are generally regarded as safe. Lipospheres and Pro-nanolipospheres are among the promising systems for the delivery of water-insoluble drugs. They are composed of aqueous dispersible particles with a rigid hydrophobic lipid centre, coated by an outer protective phospholipid exterior. These lipospheres and Pro-nanolipospheres have the advantage of being easy to scale up, high dispersibility in aqueous media, and improved physical stability, making them the perfect candidate for the delivery of different APIs using different routes including oral, parenteral, intranasal and topical routes.

Research paper thumbnail of Colloidal delivery of drugs: present strategies and conditions

Records of Pharmaceutical and Biomedical Sciences

In this report, we give a description of a broad range of colloidal drug delivery systems with sp... more In this report, we give a description of a broad range of colloidal drug delivery systems with special focus on vesicles used in research or potentially useful as carrier systems for pharmaceutical drugs or active biomolecules or as therapeutic cell carriers. Colloidal drug delivery systems provide some essential descriptions of the drug delivery systems currently being built for academic or clinical applications. This series of systems are commonly used due to outstanding drug tracking, continuous and regulated release behavior, improved drug molecules clogging performance, avoidance of product hydrolysis or enzymatic degradation, and therapeutic efficacy improvements. Such characteristics aid in the discovery of suitable carrier structures for the transmission of medicines, cells, and genes in various fields.

Research paper thumbnail of ‘Preparation and characterization of a novel mucoadhesive carvedilol nano-sponge: a promising platform for buccal antihypertensive delivery’

Purpose: Carvedilol (CRV) is a non-selective beta-blocker used for hypertension treatment, angina... more Purpose: Carvedilol (CRV) is a non-selective beta-blocker used for hypertension treatment, angina pectoris, and heart failure. Oral administration of CRV showed poor bioavailability (25%), which may be due to exposure to the first-pass metabolism. Buccal delivery was used to boost its bioavailability.Methods: In this study carboxymethylcellulose/hydroxypropyl cellulose (CMC/HPC) composite buccal sponge enriched with CRV bilosomes was developed. Bilosomes were prepared using the thin-film hydration-sonication technique by applying a 32 -factorial design.Results: BL9 possessed the highest desirability value (0.861) and therefore, it was chosen as an optimal bilosomes. It exhibited a spherical shape with 217.2 nm, 87.13% entrapment efficiency, and a sustained release of CRV up to 24h. Consecutively, BL9 was incorporated in a CMC/HPC gel and lyophilized for 24 h to obtain a CMC-HPCL9 bilosomal sponge to enhance CRV buccal delivery. Morphological analysis of the prepared sponge with impr...

Research paper thumbnail of Preparation of self-flocculated solid lipid

Journal of Research in Pharmacy, 2019

The objective of this study was to verify the effect of certain new biocompatible additive on the... more The objective of this study was to verify the effect of certain new biocompatible additive on the stability and feasibility of the SLN using Glyceryl monostearate as lipid matrix. Cationic Starch, which is newly modified in organic chemistry laboratories, used with different ratios to show the effect on zeta potential of formulated nanoparticles using Triamcinolone acetonide as a model drug. Method of High shear homogenization was used for preparation of SLN utilizing a rotor-stator homogenizer. It was found that particle diameter of formulated nanoparticles shifted from nanosized to micronized with increase of amount of cationic starch used (2.5 to 10% w/w), while the zeta potential reduced although showing high negative values (-36 to-27 mV), indicating stability. The loading capacity and encapsulation efficiency of produced nanoparticles were reduced with increase of amount of cationic starch used. The influence of cationic starch on drug release from prepared formulae was studied using dialysis bag technique. Fourier Transformation Infrared Spectroscopy (FTIR) showed the absence of new bands for loaded solid lipid nanoparticles indicating no interaction between drug and cationic starch. Electron microscope of scanning technique indicated sphere form of prepared solid lipid nanoparticles with smooth surface. It was concluded that retardation of in vitro release and effect on simulated in vivo permeation through human skin were affected by using different concentrations of cationic starch as excipient that meantime, be used to reduce zeta potential and act as self-flocculating agent during formulation.

Research paper thumbnail of Formulation and Evaluation of Etodolac Lecithin Organogel Transdermal Delivery Systems

International Journal of Pharmacy and Pharmaceutical Sciences, Feb 28, 2015

Objective: Etodolac (ETD) is a non-steroidal anti-inflammatory drug used for the acute and chroni... more Objective: Etodolac (ETD) is a non-steroidal anti-inflammatory drug used for the acute and chronic treatment of rheumatoid arthritis. It exhibits poor water solubility so its bioavailability is limited. Long term use of ETD causes serious gastrointestinal disturbance. Lecithin organogels (Los) have generated considerable interest over the years as potential topical drug delivery vehicle. Therefore, the objective of this study was to formulate ETD in lecithin organogels as a transdermal delivery system. Methods: Based on the preliminary studies, pseudoternary phase diagrams were constructed using isopropyl myristate (IPM), water and lecithin as a surfactant with different cosurfactants (CoS) and organogel areas were identified and three systems each of 36 formulae were prepared. A number of organogels were selected and loaded with 1% ETD then evaluated for visual inspection, spreadability, pH, rheological and in vitro release studies to select the optimum formulae. The selected formulae were subjected to ex-vivo permeation through excised abdominal rabbit skin and their stability was studied for one year of storage under ambient conditions. The therapeutic efficacy of ETD including analgesic activity and antiinflammatory effect was monitored. Results: The prepared ETD organogels showed suitable properties for topical application and the selected formulae (F3, F14 & F39) showed enhanced permeation. The In vivo study showed a significant difference in the therapeutic efficacy of formula F14, containing 10% IPM, 40% lecithin/PG in the ratio of (5:1) and 50% water, compared to a market product. Skin irritation test and histopathological studies proved the safety of this formula. Conclusion: So this organogel formula (F14) is considered to be a potential vehicle for a sustained release transdermal delivery system for ETD.

Research paper thumbnail of Atorvastatin-loaded pro-nanolipospheres with ameliorated oral bioavailability and antidyslipidemic activity

Despite significant advances in oral drug delivery technologies, many drugs are prone to limited ... more Despite significant advances in oral drug delivery technologies, many drugs are prone to limited oral bioavailability due to biological barriers that hinder drug absorption. Pro-nanolipospheres (PNL) are a form of delivery system that can potentiate the oral bioavailability of poorly water-soluble drugs through a variety of processes, including increased drug solubility and protecting them from degradation by intestinal or hepatic first-pass metabolism. In this study, pro-nanolipospheres were employed as a delivery vehicle for improving the oral bioavailability of the lipophilic statin, atorvastatin (ATR). Various ATR-loaded PNL formulations, composed of various pharmaceutical ingredients, were prepared by the pre-concentrate method and characterized by determining particle size, surface charge, and encapsulation efficiency. An optimized formula (ATR-PT PNL) showing the smallest particle size, highest zeta potential, and highest encapsulation efficiency was selected for further in vivo investigations. The in vivo pharmacodynamic experiments demonstrated that the optimized ATR-PT PNL formulation exerted a potent hypolipidemic effect in a Poloxamer® 407-induced hyper-lipidaemia rat model by restoring normal cholesterol and triglyceride serum levels along with alleviating serum levels of LDL while elevating serum HDL levels, compared to pure drug suspensions and marketed ATR (Lipitor®). Most importantly, oral administration of the optimized ATR-PT PNL formulation showed a dramatic increase in ATR oral bioavailability, as evinced by a 1.7- and 3.6-fold rise in systemic bioavailability when compared with oral commercial ATR suspensions (Lipitor®) and pure drug suspension, respectively. Collectively, pro-nanolipospheres might represent a promising delivery vehicle for enhancing the oral bioavailability of poorly water-soluble drugs.

Research paper thumbnail of Application of design of experiment approach for investigating the effect of partially pre-gelatinized starch on critical quality attributes of rapid orally disintegrating tablets

El-Sayed Khafagy, 2019

The objective of the current work was to enhance the critical attributes of rapid orally disinteg... more The objective of the current work was to enhance the critical attributes of rapid orally disintegrating tablets (RODTs) manufactured by direct compression technique to have sufficient mechanical strength and fast disintegration time using partially pre-gelatinized starch. A two factor, three levels (3 2), full factorial design was applied to examine the main and interaction effects of independent variables namely; partially pre-gelatinized starch level (PPGS; X 1) and microcrystalline cellulose level (MCC; X 2) on the characteristics of RODTs. The produced tablets were tested for their weight uniformity, mechanical strength, disintegration time and in-vitro drug release. Results showed that the manufactured RODTs were compiled with the USP requirements. In addition , ANOVA analysis demonstrated that PPGS level and MCC level had a significant effect (P ≤ 0.05) on the dependent responses. Furthermore, the developed RODTs showed good in-vitro/in-vivo correlation in the disintegration time. Numerical optimization using desirability approach was also applied to optimize the independent variables. It was found that the higher desirability (0.917) could be achieved at low level of PPGS (6.66%) and medium level of MCC (37.71%). Finally, it could be conclude that PPGS is a potential candidate for production of RODTs of high mechanical strength and very fast disintegration time.

Research paper thumbnail of Drug Delivery from Microsponges: A Review Article

Records of Pharmaceutical and Biomedical Sciences

Microsponges are micro-porous particles, used mainly for topical and recently for oral administra... more Microsponges are micro-porous particles, used mainly for topical and recently for oral administration. Microsponges have many advantages which make it a versatile drug delivery system. Microsponges can suspended or entrap a wide variety of substances and then be incorporated into a formulated product such as a gel, cream, liquid, or powder. Moreover, they may enhance stability, reduce side effects and modify drug release related to its porous structure which allows the active ingredient to sustain over time. The aim of this article is to provide details about microsponges including the method of preparation, characterization, mechanism of drug release from microsponges, different formulation and process factors, and a few applications about microsponges which are either proven or under research.

Research paper thumbnail of Atorvastatin-loaded pro-nanolipospheres with ameliorated oral bioavailability and antidyslipidemic activity

Colloids and Surfaces B: Biointerfaces

Despite significant advances in oral drug delivery technologies, many drugs are prone to limited ... more Despite significant advances in oral drug delivery technologies, many drugs are prone to limited oral bioavailability due to biological barriers that hinder drug absorption. Pro-nanolipospheres (PNL) are a form of delivery system that can potentiate the oral bioavailability of poorly water-soluble drugs through a variety of processes, including increased drug solubility and protecting them from degradation by intestinal or hepatic first-pass metabolism. In this study, pro-nanolipospheres were employed as a delivery vehicle for improving the oral bioavailability of the lipophilic statin, atorvastatin (ATR). Various ATR-loaded PNL formulations, composed of various pharmaceutical ingredients, were prepared by the pre-concentrate method and characterized by determining particle size, surface charge, and encapsulation efficiency. An optimized formula (ATR-PT PNL) showing the smallest particle size, highest zeta potential, and highest encapsulation efficiency was selected for further in vivo investigations. The in vivo pharmacodynamic experiments demonstrated that the optimized ATR-PT PNL formulation exerted a potent hypolipidemic effect in a Poloxamer® 407-induced hyper-lipidaemia rat model by restoring normal cholesterol and triglyceride serum levels along with alleviating serum levels of LDL while elevating serum HDL levels, compared to pure drug suspensions and marketed ATR (Lipitor®). Most importantly, oral administration of the optimized ATR-PT PNL formulation showed a dramatic increase in ATR oral bioavailability, as evinced by a 1.7- and 3.6-fold rise in systemic bioavailability when compared with oral commercial ATR suspensions (Lipitor®) and pure drug suspension, respectively. Collectively, pro-nanolipospheres might represent a promising delivery vehicle for enhancing the oral bioavailability of poorly water-soluble drugs.

Research paper thumbnail of Lipospheres and Pro-Nanolipospheres: Advancements in Drug Delivery Systems

Records of Pharmaceutical and Biomedical Sciences

The usefulness of nanotechnology nowadays in improving the performance of different active pharma... more The usefulness of nanotechnology nowadays in improving the performance of different active pharmaceutical ingredients (API) has generated a great deal of excitement worldwide. These nano-systems offer the advantage of higher bioavailability, lower toxicity, and the ability to deliver drugs with low half-life or low permeability. Lipid nano-based carriers have been extensively used for their ability to protect the API from degradation and their safety as these used lipids are generally regarded as safe. Lipospheres and Pro-nanolipospheres are among the promising systems for the delivery of water-insoluble drugs. They are composed of aqueous dispersible particles with a rigid hydrophobic lipid centre, coated by an outer protective phospholipid exterior. These lipospheres and Pro-nanolipospheres have the advantage of being easy to scale up, high dispersibility in aqueous media, and improved physical stability, making them the perfect candidate for the delivery of different APIs using different routes including oral, parenteral, intranasal and topical routes.

Research paper thumbnail of Colloidal delivery of drugs: present strategies and conditions

Records of Pharmaceutical and Biomedical Sciences

In this report, we give a description of a broad range of colloidal drug delivery systems with sp... more In this report, we give a description of a broad range of colloidal drug delivery systems with special focus on vesicles used in research or potentially useful as carrier systems for pharmaceutical drugs or active biomolecules or as therapeutic cell carriers. Colloidal drug delivery systems provide some essential descriptions of the drug delivery systems currently being built for academic or clinical applications. This series of systems are commonly used due to outstanding drug tracking, continuous and regulated release behavior, improved drug molecules clogging performance, avoidance of product hydrolysis or enzymatic degradation, and therapeutic efficacy improvements. Such characteristics aid in the discovery of suitable carrier structures for the transmission of medicines, cells, and genes in various fields.

Research paper thumbnail of ‘Preparation and characterization of a novel mucoadhesive carvedilol nano-sponge: a promising platform for buccal antihypertensive delivery’

Purpose: Carvedilol (CRV) is a non-selective beta-blocker used for hypertension treatment, angina... more Purpose: Carvedilol (CRV) is a non-selective beta-blocker used for hypertension treatment, angina pectoris, and heart failure. Oral administration of CRV showed poor bioavailability (25%), which may be due to exposure to the first-pass metabolism. Buccal delivery was used to boost its bioavailability.Methods: In this study carboxymethylcellulose/hydroxypropyl cellulose (CMC/HPC) composite buccal sponge enriched with CRV bilosomes was developed. Bilosomes were prepared using the thin-film hydration-sonication technique by applying a 32 -factorial design.Results: BL9 possessed the highest desirability value (0.861) and therefore, it was chosen as an optimal bilosomes. It exhibited a spherical shape with 217.2 nm, 87.13% entrapment efficiency, and a sustained release of CRV up to 24h. Consecutively, BL9 was incorporated in a CMC/HPC gel and lyophilized for 24 h to obtain a CMC-HPCL9 bilosomal sponge to enhance CRV buccal delivery. Morphological analysis of the prepared sponge with impr...

Research paper thumbnail of Preparation of self-flocculated solid lipid

Journal of Research in Pharmacy, 2019

The objective of this study was to verify the effect of certain new biocompatible additive on the... more The objective of this study was to verify the effect of certain new biocompatible additive on the stability and feasibility of the SLN using Glyceryl monostearate as lipid matrix. Cationic Starch, which is newly modified in organic chemistry laboratories, used with different ratios to show the effect on zeta potential of formulated nanoparticles using Triamcinolone acetonide as a model drug. Method of High shear homogenization was used for preparation of SLN utilizing a rotor-stator homogenizer. It was found that particle diameter of formulated nanoparticles shifted from nanosized to micronized with increase of amount of cationic starch used (2.5 to 10% w/w), while the zeta potential reduced although showing high negative values (-36 to-27 mV), indicating stability. The loading capacity and encapsulation efficiency of produced nanoparticles were reduced with increase of amount of cationic starch used. The influence of cationic starch on drug release from prepared formulae was studied using dialysis bag technique. Fourier Transformation Infrared Spectroscopy (FTIR) showed the absence of new bands for loaded solid lipid nanoparticles indicating no interaction between drug and cationic starch. Electron microscope of scanning technique indicated sphere form of prepared solid lipid nanoparticles with smooth surface. It was concluded that retardation of in vitro release and effect on simulated in vivo permeation through human skin were affected by using different concentrations of cationic starch as excipient that meantime, be used to reduce zeta potential and act as self-flocculating agent during formulation.

Research paper thumbnail of Formulation and Evaluation of Etodolac Lecithin Organogel Transdermal Delivery Systems

International Journal of Pharmacy and Pharmaceutical Sciences, Feb 28, 2015

Objective: Etodolac (ETD) is a non-steroidal anti-inflammatory drug used for the acute and chroni... more Objective: Etodolac (ETD) is a non-steroidal anti-inflammatory drug used for the acute and chronic treatment of rheumatoid arthritis. It exhibits poor water solubility so its bioavailability is limited. Long term use of ETD causes serious gastrointestinal disturbance. Lecithin organogels (Los) have generated considerable interest over the years as potential topical drug delivery vehicle. Therefore, the objective of this study was to formulate ETD in lecithin organogels as a transdermal delivery system. Methods: Based on the preliminary studies, pseudoternary phase diagrams were constructed using isopropyl myristate (IPM), water and lecithin as a surfactant with different cosurfactants (CoS) and organogel areas were identified and three systems each of 36 formulae were prepared. A number of organogels were selected and loaded with 1% ETD then evaluated for visual inspection, spreadability, pH, rheological and in vitro release studies to select the optimum formulae. The selected formulae were subjected to ex-vivo permeation through excised abdominal rabbit skin and their stability was studied for one year of storage under ambient conditions. The therapeutic efficacy of ETD including analgesic activity and antiinflammatory effect was monitored. Results: The prepared ETD organogels showed suitable properties for topical application and the selected formulae (F3, F14 & F39) showed enhanced permeation. The In vivo study showed a significant difference in the therapeutic efficacy of formula F14, containing 10% IPM, 40% lecithin/PG in the ratio of (5:1) and 50% water, compared to a market product. Skin irritation test and histopathological studies proved the safety of this formula. Conclusion: So this organogel formula (F14) is considered to be a potential vehicle for a sustained release transdermal delivery system for ETD.

Research paper thumbnail of Atorvastatin-loaded pro-nanolipospheres with ameliorated oral bioavailability and antidyslipidemic activity

Despite significant advances in oral drug delivery technologies, many drugs are prone to limited ... more Despite significant advances in oral drug delivery technologies, many drugs are prone to limited oral bioavailability due to biological barriers that hinder drug absorption. Pro-nanolipospheres (PNL) are a form of delivery system that can potentiate the oral bioavailability of poorly water-soluble drugs through a variety of processes, including increased drug solubility and protecting them from degradation by intestinal or hepatic first-pass metabolism. In this study, pro-nanolipospheres were employed as a delivery vehicle for improving the oral bioavailability of the lipophilic statin, atorvastatin (ATR). Various ATR-loaded PNL formulations, composed of various pharmaceutical ingredients, were prepared by the pre-concentrate method and characterized by determining particle size, surface charge, and encapsulation efficiency. An optimized formula (ATR-PT PNL) showing the smallest particle size, highest zeta potential, and highest encapsulation efficiency was selected for further in vivo investigations. The in vivo pharmacodynamic experiments demonstrated that the optimized ATR-PT PNL formulation exerted a potent hypolipidemic effect in a Poloxamer® 407-induced hyper-lipidaemia rat model by restoring normal cholesterol and triglyceride serum levels along with alleviating serum levels of LDL while elevating serum HDL levels, compared to pure drug suspensions and marketed ATR (Lipitor®). Most importantly, oral administration of the optimized ATR-PT PNL formulation showed a dramatic increase in ATR oral bioavailability, as evinced by a 1.7- and 3.6-fold rise in systemic bioavailability when compared with oral commercial ATR suspensions (Lipitor®) and pure drug suspension, respectively. Collectively, pro-nanolipospheres might represent a promising delivery vehicle for enhancing the oral bioavailability of poorly water-soluble drugs.

Research paper thumbnail of Application of design of experiment approach for investigating the effect of partially pre-gelatinized starch on critical quality attributes of rapid orally disintegrating tablets

El-Sayed Khafagy, 2019

The objective of the current work was to enhance the critical attributes of rapid orally disinteg... more The objective of the current work was to enhance the critical attributes of rapid orally disintegrating tablets (RODTs) manufactured by direct compression technique to have sufficient mechanical strength and fast disintegration time using partially pre-gelatinized starch. A two factor, three levels (3 2), full factorial design was applied to examine the main and interaction effects of independent variables namely; partially pre-gelatinized starch level (PPGS; X 1) and microcrystalline cellulose level (MCC; X 2) on the characteristics of RODTs. The produced tablets were tested for their weight uniformity, mechanical strength, disintegration time and in-vitro drug release. Results showed that the manufactured RODTs were compiled with the USP requirements. In addition , ANOVA analysis demonstrated that PPGS level and MCC level had a significant effect (P ≤ 0.05) on the dependent responses. Furthermore, the developed RODTs showed good in-vitro/in-vivo correlation in the disintegration time. Numerical optimization using desirability approach was also applied to optimize the independent variables. It was found that the higher desirability (0.917) could be achieved at low level of PPGS (6.66%) and medium level of MCC (37.71%). Finally, it could be conclude that PPGS is a potential candidate for production of RODTs of high mechanical strength and very fast disintegration time.