Papers by Dr-Kifayat Ullah Shah
ABSTRACT Introduction: Lipid-based drug delivery systems (LBDDS) are the most promising technique... more ABSTRACT Introduction: Lipid-based drug delivery systems (LBDDS) are the most promising technique to formulate the poorly water soluble drugs. Nanotechnology strongly influences the therapeutic performance of hydrophobic drugs and has become an essential approach in drug delivery research. Self-nanoemulsifying drug delivery systems (SNEDDS) are a vital strategy that combines benefits of LBDDS and nanotechnology. SNEDDS are now preferred to improve the formulation of drugs with poor aqueous solubility. Areas covered: The review in its first part shortly describes the LBDDS, nanoemulsions and clarifies the ambiguity between nanoemulsions and microemulsions. In the second part, the review discusses SNEDDS and elaborates on the current developments and modifications in this area without discussing their associated preparation techniques and excipient properties. Expert opinion: SNEDDS have exhibit the potential to increase the bioavailability of poorly water soluble drugs. The stability of SNEDDS is further increased by solidification. Controlled release and supersaturation can be achieved, and are associated with increased patient compliance and improved drug loads, respectively. Presence of biodegradable ingredients and ease of large-scale manufacturing combined with a lot of 'drug-targeting opportunities' give SNEDDS a clear distinction and prominence over other solubility enhancement techniques.
The objective of this study was to develop directly compressed oral controlled-release ibuprofen ... more The objective of this study was to develop directly compressed oral controlled-release ibuprofen matrix tablets containing hydrophobic polymer (Ethocel ®) of different viscosity gardes (Ethocel ® standard 7P, 7FP, 10P, 10FP 100P and 100FP). As ibuprofen like other non-steroidal anti-inflammatory drugs has dosage frequency and severe gastrointestinal tract (GIT) complications and patient non-compliance, so to avoid these problems, controlled release matrices were developed. Before development of matrix tablets, pre-formulation studies were performed for the determination of physicochemical interaction between polymer, drug and co-excipients, using differential scanning calorimetry (DSC) and Fourier transform infrared (FT-IR) and no interaction was found. Controlled-release matrix tablets were formulated by direct compression method. Effect of partial replacement of lactose by different co-excipients such as HPMC K100M, starch and CMC on the release of drug was also studied. The tablets were subjected to different physicochemical, dimensional and quality controlled tests, such as drug content, weight variations, friability, hardness, thickness and diameter, all these tests were within United Stated Pharmacopoeia (USP) range. The in vitro release profile in phosphate buffer (pH 7.4) for all formulations containing polymer and co-excipients was compared with a formulation developed without polymer and co-excipients for 24 h. Different kinetics models were used, such as first-order equation, zero-order equation, Higuachi equation, Hixon Crowel's equation and Korsmeyer-Peppas to study and investigate the release mechanism. It was concluded that formulations containing different grades of ethylcellulose polymer showed prolonged release for 6 to 18 h, but the formulation containing polymer Ethocel ® standard FP7 premium without co-excipient showed controlled release for 24 h, which can be used to develop controlled release matrices of ibuprofen with optimum release kinetics. All those formulations containing co-excipients showed enhanced release rate.
The study aims to design once-daily controlled release hydrophilic hydrophobic matrix tablets of ... more The study aims to design once-daily controlled release hydrophilic hydrophobic matrix tablets of flurbiprofen with cellulose derivative polymers using direct compression technique. Preformulation factors including bulk density, tapped density, Hausner’s factor, angle of repose and compressibility index were evaluated for flurbiprofen powder drug and physical mixtures. Tablets were compressed using a single punch machine and various physical parameters were tested including hardness, friability, weight variation, content uniformity, thickness and diameter. All of the tests for starting material fell in the acceptable British Pharmacopoeial limits. In-vitro release study was conducted in phosphate buffer solution, pH 7.4 and different kinetics parameters were applied on dissolution data. Dissolution study showed a controlled release profile for formulations F-1 and F-2, containing ethylcellulose and hydroxypropylmethylcellulose and released 98.29 and 97.49% drug after 12 and 18 hrs, respectively. The release exponent, “n” for F-1 and F-2 indicated an anomalous release behavior with the values 0.599 and 0.776 and the linearity of 0.986 and 0.971, respectively
The objective of the study was to formulate and evaluate controlled release polymeric tablets of ... more The objective of the study was to formulate and evaluate controlled release polymeric tablets of Diclofenac Potassium for the release rate, release patterns and the mechanism involved in the release process of the drug. Formulations with different types and grades of Ethyl Cellulose Ether derivatives in several drug-to-polymer ratios (D:P) were compressed into tablets using the direct compression method. In vitro drug release studies were performed in phosphate buffer (pH 7.4) as dissolution medium by using USP Method-1 (Rotating Basket Method). Similarity factor f 2 and dissimilarity factor f 1 were applied for checking the similarities and dissimilarities of the release profiles of different formulations. For the determination of the release mechanism and drug release kinetics various mathematical / kinetic models were employed. It was found that all of the Ethocel polymers could significantly slow down the drug release rate with Ethocel FP polymers being the most efficient, especially at D:P ratios of 10:03 which lead towards the achievement of zero or near zero order release kinetics.
The aim of the present study was the formulation and evaluation of controlled release polymeric t... more The aim of the present study was the formulation and evaluation of controlled release polymeric tablets of Diclofenac Potassium by wet granulation method for the release rate, release pattern and the mechanism involved in drug release. Formulations having three grades of polymer Ethocel (7P; 7FP, 10P, 10FP, 100P, 100FP) in several drugs to polymer ratios (10:3 and 10:1) were compressed into tablets using wet granulation method. Co-excipients were added to some selected formulations to investigate their enhancement effect on in vitro drug release patterns. In vitro drug release studies were performed using USP Method-1 (Rotating Basket method) and Phosphate buffer (pH 7.4) was used as a dissolution medium. The similarities and dissimilarities of release profiles of test formulations with reference standard were checked using f2 similarity factor and f1 dissimilarity factor. Mathematical/Kinetic models were employed to determine the release mechanism and drug release kinetics.
The present study was conducted to formulate and evaluate flurbiprofen transdermal gel. A standar... more The present study was conducted to formulate and evaluate flurbiprofen transdermal gel. A standard calibration curve was constructed to obtain a regression line equation to be used for finding out the concentration of drug in samples. Olive oil was used as penetration enhancer and was added in different concentrations to some selected formulations to see its enhancement effect on in vitro drug release profiles. The prepared gels were evaluated for several physico-chemical parameters to justify their suitability for topical use. The in vitro drug release studies were carried out by using Franz cell diffusion apparatus across both synthetic membrane and excised albino rabbit skin. In order to investigate the drug release mechanism a kinetic approach was made by employing Korsmeyer kinetic model to the in vitro drug release profiles of flurbiprofen. The flurbiprofen topical gels were successfully prepared and could be beneficial for topical use.
The aim of the study was to formulate and evaluate topically applied ketoprofen gels and patches ... more The aim of the study was to formulate and evaluate topically applied ketoprofen gels and patches and to see the effect of naturally occurring almond oil as penetration enhancer on the penetration of ketoprofen through artificial membrane/rabbit skin. Prior to ketoprofen gel and patch formulation, the particle size and particle size determination of ketoprofen was analyzed by Particle size analyzer (Horiba LA300). Ketoprofen gels and patches were formulated and almond oil was added in several concentrations i.e. 0.5%, 1%, 1.5%, 2%, 2.5% and 3%. The formulated gels were evaluated by several parameters like pH, spreadibility, consistency, homogeneity, skin irritation and drug content determination. In vitro drug permeation studies from transdermal gels and patches were carried out across artificial membrane and rabbit skin by using Franz Cell Apparatus (PermeGear, USA). Kinetics model was employed to the release patterns of ketoprofen from gel and patches in order to investigate the drug transport mechanism. The cumulative amount of drug penetrated from different formulations was statistically evaluated by using One-way analysis of variance (ANOVA). Stability study was performed for various batches of ketoprofen transdermal gel. Almond oil as penetration enhancer in various concentrations significantly enhances the penetration of drug from transdermal gels and patch across synthetic membrane/rabbit skin but was most significant when used in 3% concentration.
The seeds of Nigella sativa have been used in folk medicine all over the world. The plant has bee... more The seeds of Nigella sativa have been used in folk medicine all over the world. The plant has been of interest due to its low degree of toxicity and beneficial pharmacological properties like antihypertensive, hypoglycemic, antifungal, anti-inflammatory, antihistaminic, antioxidant, along with significant anti-neuplastic activities. The present clinical study was undertaken to ascertain the adjuvant effect of Nigella seeds on various clinical and biochemical parameters of metabolic syndrome. After final diagnosis and considering inclusion and exclusion criteria, one hundred and fifty nine patients were enrolled in this study. Patients were divided into two groups. In Group I (standard group), patients were advised to take simvastatin 10 mg once a day, metformin 500 mg twice a day, Enalapril 10 mg once a day, Atenolol 50 mg once a day and clopidagrel 75 mg once a day for a period of six weeks. In Group II (Nigella seeds group), patients were advised the above standard medication plus Nigella seeds 250 mg twice daily for a period of six weeks. Blood sugar both fasting and postprandial, fasting lipid profile and different parameters of obesity were recorded before therapy and after completion of therapy. It was found that the addition of Nigella seeds provide beneficial effects in all the clinical and biochemical parameters for the adult's treatment panel-III of metabolic disorders especially in fasting blood sugar, low density lipoproteins and high density lipoproteins. No sign of toxicity of the plant appeared in the Group II. Improvement in all other parameters like blood pressure, circumference of waist and serum triglyceride was also observed. Thus, Nigella seeds were found to be effective as an adjuvant therapy in patients of dyslipidemia and hyperglycemia.
SUMMARY. Controlled release dosage forms have both predictability and reproducibility in the drug... more SUMMARY. Controlled release dosage forms have both predictability and reproducibility in the drug release rates and reduces dosage frequency and improves patient compliance. In this research work, controlled release matrix tablets of flurbiprofen were designed and developed by using polymers Ethocel grade 7 (Ethocel 7 premium and Ethocel 7 FP) as rate controlling polymers. The tablets formulations were done at drug-to-polymer ratio (D:P) of 10:3 and in some selected formulations co-excipients such as hy-droxyproply methyl cellulose (HPMC) carboxymethyl cellulose (CMC) and starch were added to check its effect on drug release rates. Tablets were compressed by direct compression method. Dissolution studies were conducted in 0.2 M phosphate buffer (pH 7.2) using USP Method-I (rotating basket method) in eight stationed pharma test dissolution apparatus. The release mechanisms of drug were determined by applying kinetic models such as zero-order, 1st-order, Highuchi, Hixson Crowell and Power law. Similarity factor (f 2) was applied to determine dissolution profiles equivalency between test formulations and reference standard Froben® SR (sustained release) formulation. The tablets containing polymer Ethocel 7 FP Premium extended the drug release rate proficiently than the Ethocel 7 Premium and this could be due to its small particles size. Both formulations released the drug by anomalous, non-fickian diffusion. The drug release rates were also increased by co-excipients in the selected formulations. In the designing and de-volvement of controlled release matrix tablets, polymers Ethocel 7 Premium and Ethocel 7 FP Premium can be used successfully as rate controlling agents.
This study presents sustained releasemicroencapsulation of Diltiazem HCL. Its in-vitro dissolutio... more This study presents sustained releasemicroencapsulation of Diltiazem HCL. Its in-vitro dissolution study in phosphate buffer pH 7.4 as dissolution medium and in vivo behaviour in animal subjects. The microcapsules were prepared using polymers Ethocel 7P and Ethocel 7FP at two different drug to polymer (D: P) ratios i.e. 1:5 and 1:10 and the effect of concentration was observed on drug release behaviour. The prepared microcapsules were evaluated for different physical characteristics i.e. Bulk density, Tap density, Compressibility index, Hausner's ratio and Angle of repose. Characterization of the developed microcapsules was carried out using Differential Scanning Calorimetery and Fourier Transform Infrared Spectroscopy while Scanning Electron Microscopy was performed to observe the morphology of the microcapsules. Model dependent and in dependent approaches were used to find out the drug transport mechanism and to compare the drug release profiles with standard formulation respectively. All the formulations show anomalous, non-Fickian diffusion mechanism and the data was best fitted in Korsmeyer'sPeppas equation. While carrying out in vivo studies, simple and rapid HPLC methods were developed which revealed optimum serum concentration (Cmax) levels for the developed microcapsules predicting least chances of side or adverse effects.
Abstract:
Introduction: Thiomers are the product of the immobilization of sulfhydryl-bearing lig... more Abstract:
Introduction: Thiomers are the product of the immobilization of sulfhydryl-bearing ligands onto the polymer backbone of a conventional polymer, which results in a significant improvement in mucoadhesion; in situ gelation and efflux inhibition compare with unchanged polymers. Because of thiol groups, thiomers have more reactivity and enhanced protection against oxidation. Since the late 1990s, extensive work has been conducted on these promising polymeric excipients in the pharmaceutical field.
Areas Covered: This review covers thiomers, their classification and their different properties. Various techniques for the synthesis, purification and characterization of thiomers are described in detail. This review also encompasses their various properties such as mucoadhesion, permeation enhancement, in situ gelation and efflux inhibition, as well as different formulations based on thiomers. In addition to the use of thiomers as multifunctional excipients, this review also encompasses their use as drugs.
Expert Opinion: The synthesis is realized by linkage of sulfhydryl-bearing ligands but reported methods give low yields. Higher degrees of modification are not necessary and would probably lead to extreme changes in properties. Nevertheless, an accurate characterization of the final product is important. The scale-up procedure for industrial manufacturing has been adapted to produce GMP materials; Lacrimera® eye drops have already entered the European market.
Being controlled release dosage forms, tablets allow an improved absorption and release profiles ... more Being controlled release dosage forms, tablets allow an improved absorption and release profiles of Ofloxacin. The fact that drugs with fine particles size can be compressed well after wetting, so in our research studies Ofloxacin controlled release matrix tablets were prepared by wet granulation technique. In order to investigate the potential of Ethyl cellulose ether derivatives as a matrix material, Ofloxacin formulations with different types and grades of Ethocel were prepared at several drug-to-polymer ratios. The method adopted for in vitro drug release studies was USP Method-1 (rotating Basket Method) by Pharma test dissolution apparatus using phosphate buffer 7.4 pH as a dissolution medium. Various Kinetic models were employed to the formulations for the purpose of determination of release mechanism. A comparative study was performed between the tested Ofloxacin-Ethocel formulations and a standard reference obtained from the local market. F 1 dissimilarity factor and f 2 similarity factor were applied to the formulations for the checking of dissimilarities and similarities between the tested formulations and reference standard.
Lipid-based drug delivery systems (LBDDS) are the most promising technique to formulate the poorl... more Lipid-based drug delivery systems (LBDDS) are the most promising technique to formulate the poorly water soluble drugs. Nanotechnology strongly influences the therapeutic performance of hydrophobic drugs and has become an essential approach in drug delivery research. Self-nanoemulsifying drug delivery systems (SNEDDS) are a vital strategy that combines benefits of LBDDS and nanotechnology. SNEDDS are now preferred to improve the formulation of drugs with poor aqueous solubility.
The objective of the study was to formulate and evaluate sustained release polymeric tablets of k... more The objective of the study was to formulate and evaluate sustained release polymeric tablets of ketoprofen for the release rate, release patterns and the mechanism involved in the release process of the drug. Formulations with three different types of newly synthesized polymers and one grade of ethyl cellulose ether derivatives (FP100 premium) in several drug-to-polymer ratios (D:P ratio 10:1, 10:2 and 10:3) were compressed into tablets using the direct compression method. They were examined for their physical properties and appearance. Tablets dimensional tests (thickness, diameter) and Q.C tests (hardness, friability, disintegration) were performed according to the USP methods. For in vitro drug release studies of Ketoprofen controlled release (CR) tablets, the USP Method-1 (Rotating Basket Method) was used with Pharma test dissolution apparatus (D-63512 Hainburg, Germany). The medium used for dissolution was phosphate buffer having a pH of 7.4 kept at constant temperature of 37±1°C. In order to analyze the drug release kinetics from each of the prepared matrices, five different mathematical models were applied to the release data including zero order kinetics, first order kinetics, Higuchi kinetics, Hixson Crowell kinetics and Korsmeyer Peppas equations were applied to the release data. The results obtained from different parameters showed that polymers: Polyglycolide, PGA-cocaprolactone, PGA-co-pentadecalactone and Ethocel FP100 premium can be used successfully in order to develop directly compressed prolonged release tablets of slightly soluble drugs such as ketoprofen. Particle size of polymer is a determining factor in controlling the release of ketoprofen from tablets. Ethocel standard FP100 polymers extend the release rates of drug more efficiently than the conventional granular form of the other three polymers. Further, the three new polymers and Ethocel FP100 could efficiently extend the release of the drugs as compared to the reference conventional formulation.
To formulate and prepare controlled release (CR) matrix tablets of tramadol HCl using Carbopol 97... more To formulate and prepare controlled release (CR) matrix tablets of tramadol HCl using Carbopol 974P and 934 polymers as rate-controlling agents. Methods: The tablets were prepared by direct compression method using various drug to polymer (D:P) ratios. Co-excipients, including carboxymethylcellulose, starch and/or hydroxypropyl methylcellulose were also used to modulate the formulations. Various physical tests and in vitro dissolution studies were carried out on the formulations. The dissolution data were subjected to various release models Results: As the concentration of the polymer (rate-controlling agent) increased, dissolution rate decreased, For the formulation containing Carbopol 974P at D:P ratio of 10:7, drug release decreased to 83 % compared with the release rate of 99 % for the formulation with D:P ratio of 10:3. Kinetic analysis indicates that drug release mechanism was anomalous non-Fickian diffusion. Conclusion: Both Carbopol 974P and 934 can be used as rate-controlling agents in the formulation of tramadol HCl CR tablets. Appropriate selection of drug/polymer ratio can be applied effectively to modulate the dissolution rate of the drug.
To formulate and prepare controlled release (CR) matrix tablets of tramadol HCl using Carbopol 97... more To formulate and prepare controlled release (CR) matrix tablets of tramadol HCl using Carbopol 974P and 934 polymers as rate-controlling agents. Methods: The tablets were prepared by direct compression method using various drug to polymer (D:P) ratios. Co-excipients, including carboxymethylcellulose, starch and/or hydroxypropyl methylcellulose were also used to modulate the formulations. Various physical tests and in vitro dissolution studies were carried out on the formulations. The dissolution data were subjected to various release models Results: As the concentration of the polymer (rate-controlling agent) increased, dissolution rate decreased, For the formulation containing Carbopol 974P at D:P ratio of 10:7, drug release decreased to 83 % compared with the release rate of 99 % for the formulation with D:P ratio of 10:3. Kinetic analysis indicates that drug release mechanism was anomalous non-Fickian diffusion. Conclusion: Both Carbopol 974P and 934 can be used as rate-controlling agents in the formulation of tramadol HCl CR tablets. Appropriate selection of drug/polymer ratio can be applied effectively to modulate the dissolution rate of the drug.
Uploads
Papers by Dr-Kifayat Ullah Shah
Introduction: Thiomers are the product of the immobilization of sulfhydryl-bearing ligands onto the polymer backbone of a conventional polymer, which results in a significant improvement in mucoadhesion; in situ gelation and efflux inhibition compare with unchanged polymers. Because of thiol groups, thiomers have more reactivity and enhanced protection against oxidation. Since the late 1990s, extensive work has been conducted on these promising polymeric excipients in the pharmaceutical field.
Areas Covered: This review covers thiomers, their classification and their different properties. Various techniques for the synthesis, purification and characterization of thiomers are described in detail. This review also encompasses their various properties such as mucoadhesion, permeation enhancement, in situ gelation and efflux inhibition, as well as different formulations based on thiomers. In addition to the use of thiomers as multifunctional excipients, this review also encompasses their use as drugs.
Expert Opinion: The synthesis is realized by linkage of sulfhydryl-bearing ligands but reported methods give low yields. Higher degrees of modification are not necessary and would probably lead to extreme changes in properties. Nevertheless, an accurate characterization of the final product is important. The scale-up procedure for industrial manufacturing has been adapted to produce GMP materials; Lacrimera® eye drops have already entered the European market.
Introduction: Thiomers are the product of the immobilization of sulfhydryl-bearing ligands onto the polymer backbone of a conventional polymer, which results in a significant improvement in mucoadhesion; in situ gelation and efflux inhibition compare with unchanged polymers. Because of thiol groups, thiomers have more reactivity and enhanced protection against oxidation. Since the late 1990s, extensive work has been conducted on these promising polymeric excipients in the pharmaceutical field.
Areas Covered: This review covers thiomers, their classification and their different properties. Various techniques for the synthesis, purification and characterization of thiomers are described in detail. This review also encompasses their various properties such as mucoadhesion, permeation enhancement, in situ gelation and efflux inhibition, as well as different formulations based on thiomers. In addition to the use of thiomers as multifunctional excipients, this review also encompasses their use as drugs.
Expert Opinion: The synthesis is realized by linkage of sulfhydryl-bearing ligands but reported methods give low yields. Higher degrees of modification are not necessary and would probably lead to extreme changes in properties. Nevertheless, an accurate characterization of the final product is important. The scale-up procedure for industrial manufacturing has been adapted to produce GMP materials; Lacrimera® eye drops have already entered the European market.