Methods and Findings in Experimental and Clinical Pharmacology, 2008
The aim of this study was to investigate and evaluate a microemulsion gel-based system of babchi ... more The aim of this study was to investigate and evaluate a microemulsion gel-based system of babchi oil (Psoralea corylifolia) for the treatment of psoriasis, which could provide improved permeation of the drug through the skin and increased patient compliance. Babchi oil is used because its chief constituent psoralen is a photoactive furocoumarin that binds to DNA when exposed to UV light to form photoproducts with pyrimidine base. This action inhibits DNA synthesis and causes decrease in cell proliferation. Moreover, babchi oil, in addition to providing psoralen, also acts as an oily phase for microemulsion system. The presence of surfactant and cosurfactant increases the permeation. On the basis of qualitative and quantitative estimation of all eight brands of babchi oil, Bakuchi Tail was selected for microemulsion formulation. Microemulsions were prepared by aqueous phase-titration method. Pseudoternary phase diagrams were constructed for the identification of microemulsion existence zones. Prepared microemulsions were subjected to different thermodynamic stability tests and characterized for droplet size, viscosity and refractive index. In vitro skin permeation of babchi oil through rat abdominal skin was determined by the Franz diffusion cell. The in vitro skin permeation profile of formulation F2, which consisted of 1.67% v/v of babchi oil, 8.33% v/v of oleic acid, S(mix) 55% v/v of Tween 80 Transcutol-P (S/Co ratio 1:1) and 35% v/v of distilled water, was significant when compared with other microemulsion formulations (p < 0.05). Formulation F2 was converted into microemulsion gel by adding 1% Carbopol-940 and coded as MGF2. Formulation MGF2 was selected for its in vivo antiinflammatory effects determined by footpad edema. The results suggested that microemulsion gel is a potential vehicle for improved topical delivery of psoralen and that microemulsion gels are potential vehicles for improved topical delivery of babchi oil.
A quantitative method using precoated silica gel-60 Lichrosphere highperformance thin-layer chrom... more A quantitative method using precoated silica gel-60 Lichrosphere highperformance thin-layer chromatography (HPTLC) plates, automated band wise sample application, and n-hexane:acetone:formic acid (2:1:0.025 v/v/v) as mobile phase, has been developed and validated for the analysis of psoralen in marketed formulations and novel solid lipid nanoparticles (SLNs). Densitometric analysis was performed at 250 nm in absorbance mode. Compact bands of psoralen were obtained at R f 0.32 ± 0.02. The method was validated for linearity, precision, robustness, sensitivity, specificity, and recovery. Linearity (r 2 = 0.995), limit of detection (8.0 ng band −1), limit of quantification (18.1 ng band −1), recovery (98.06-99.64%), and precision (≤0.74) were satisfactory. Statistical analysis established that the developed method for quantification of psoralen in marketed formulation and from solid lipid nanoparticles is reproducible and selective.
A simple, selective, precise, accurate, and cost-effective thin-layer chromatographic (TLC) metho... more A simple, selective, precise, accurate, and cost-effective thin-layer chromatographic (TLC) method for analysis of psoralen in different brands of babchi (Psoralea corylifolia) oil has been developed and validated. Aluminium TLC plates precoated with silica gel 60F 254 were used as the stationary phase and n-hexane-acetone-formic acid 2:1:0.025 (v/v) as mobile phase. A compact, resolved psoralen peak (R F value 0.32 ± 0.02) was observed by densitometric analysis in absorbance mode at 250 nm. Calibration data revealed a good linear relationship (r 2 = 0.9956) between peak area and concentration in the range 20-200 ng per spot. Mean ± SD values of slope and intercept were 11.35 ± 0.36 and 14.64 ± 0.31, respectively. Statistical analysis proved the method to be a repeatable, selective, and accurate means of estimation of psoralen in different brands of babchi oil.
Our knowledge in the field of ocular drug delivery is rapidly expanding. An increase in the under... more Our knowledge in the field of ocular drug delivery is rapidly expanding. An increase in the understanding of ocular drug absorption and disposition vis-à-vis developments in nanotechnology has led to the emergence of many of the nanotechnology-based ocular drug delivery systems including nanoparticles, microemulsions, liposomes, solid lipid nanoparticles, light-sensitive nanocarrier systems, etc. The need to develop effective treatments for posterior eye segment diseases is more important than surface delivery. Treatment of blinding diseases of the eye, such as proliferative retinopathy or macular degeneration, requires effective and safe delivery of drugs to posterior eye segment tissues, and recent advances in nanotechnology have demonstrated successful outcomes. Nanoscientists should focus their efforts on nano-ophthalmology. This review describes the current status and progress made so far, and the course that needs to be pursued in the future.
In the present study, spherical microspheres able to prolong the release of INH were produced by ... more In the present study, spherical microspheres able to prolong the release of INH were produced by a modified emulsification method, using sodium alginate as the hydrophilic carrier. The shape and surface characteristics were determined by scanning electron microscopy using gold sputter technique. Particle sizes of both placebo and drug-loaded formulations were measured by SEM and the particle size distribution was determined by an optical microscope. The physical state of the drug in the formulation was determined by differential scanning calorimetry (DSC). The release profiles of INH from microspheres were examined in simulated gastric fluid (SGF pH 1.2) and simulated intestinal fluid (SIF pH 7.4). Gamma-scintigraphic studies were carried out to determine the location of microspheres on oral administration and the extent of transit through the gastrointestinal tract (GIT). The microspheres had a smoother surface and were found to be discreet and spherical in shape. The particles were heterogeneous with the maximum particles of an average size of 3.719 m. Results indicated that the mean particle size of the microspheres increased with an increase in the concentration of polymer and the cross-linker as well as the cross-linking time. The entrapment efficiency was found to be in the range of 40-91%. Concentration of the cross-linker up to 7.5% caused increase in the entrapment efficiency and the extent of drug release. Optimized isoniazid-alginate microspheres were found to possess good bioadhesion (72.25 ± 1.015%). The bioadhesive property of the particles resulted in prolonged retention in the small intestine. Microspheres could be observed in the intestinal lumen at 4 h and were detectable in the intestine 24 h post-oral administration, although the percent radioactivity had significantly decreased (t 1/2 of 99m Tc = 4-5 h). Increased drug loading (91%) was observed for the optimized formulation suggesting the efficiency of the method. Nearly 26% of INH was released in SGF pH 1.2 in 6 h and 71.25% in SIF pH 7.4 in 30 h. No significant drug-polymer interactions were observed in FT-IR studies. Dissolution and ␥-scintigraphy studies have shown promising results proving the utility of the formulation for enteric drug delivery.
The objective of the present study was to investigate the effect of various terpenes, including a... more The objective of the present study was to investigate the effect of various terpenes, including a diterpene, forskolin (FSK; a putative penetration enhancer), on skin permeation of valsartan. Permeation studies were carried out with Automated Transdermal Diffusion Cells Sampling System (SFDC 6, LOGAN Instruments Corp., NJ, USA) through rat skin and human cadaver skin (HCS) using ethanol: IPB (pH 7.4) (40:60) as vehicle. The efficacy of the study terpenes for permeation of valsartan across rat skin and human cadaver skin was found in the order of cineole > d-limonene > l-menthol > linalool > FSK and cineole > d-limonene > linalool > l-menthol > FSK, respectively. No apparent skin irritation (erythema, edema) was observed on treatment of skin with terpenes including FSK. FT-IR, DSC, and histopathological studies revealed that FSK enhanced the skin permeation of the active drug by disruption and extraction of lipid bilayers of SC in consonance with other terpenes.
International journal of pharmaceutics, Jan 25, 2013
The aim of the current investigation is to develop and statistically optimize nanoethosomes for t... more The aim of the current investigation is to develop and statistically optimize nanoethosomes for transdermal valsartan delivery. Box-Behnken experimental design was applied for optimization of nanoethosomes. The Independent variables were phospholipids 90G (X(1)), ethanol (X(2)), valsartan (X(3)) and sonication Time (X(4)) while entrapment efficiency (Y(1)), vesicle size (Y(2)) and flux (Y(3)) were the dependent variables. The optimized formulation obtained was then tested in rats for an in vivo pharmacokinetic study. Results indicate that the nanoethosomes of valsartan provides better flux, reasonable entrapment efficiency, more effectiveness for transdermal delivery as compared to rigid liposomes. Optimized nanoethosomal formulation with mean particle size is 103±5.0nm showed 89.34±2.54% entrapment efficiency and achieved mean transdermal flux 801.36±21.45μg/cm(2)/hr. Nanoethosomes proved significantly superior in terms of, amount of drug permeated in the skin, with an enhancement ...
The major purpose of this study was to develop and characterize a series of carbopol- and methyl ... more The major purpose of this study was to develop and characterize a series of carbopol- and methyl cellulose-based solutions as the in situ gelling vehicles for ophthalmic drug delivery. The rheological properties, in vitro release as well as in vivo pharmacological response of a combination of polymer solutions, including carbopol and methyl cellulose, were evaluated. It was found that the optimum concentration of carbopol solution for the in situ gel-forming delivery systems was 0.3% (w/w), and that for methyl cellulose solution was 1.5% (w/w). The mixture of 0.3% carbopol and 1.5% methyl cellulose solutions showed a significant enhancement in gel strength in the physiological condition; this gel mixture was also found to be free flowing at pH 4.0 and 25 degrees C. The rheological behaviors of carbopol/methyl cellulose solution were not affected by the incorporation of the drug. Drug levels in the aqueous humor of the rabbits were well above the MIC-values of relevant bacteria after 12 hours, the results of an optimized formulation containing 0.18% of pefloxacin mesylate compared well with the 0.3% marketed eye drop formulation, indicating our formulation to be significantly better considering that a similar effect was obtained at half the concentration. Both the in vitro release and in vivo pharmacological studies indicated that the carbopol/methyl cellulose solution had better ability to retain drug than did the carbopol or methyl cellulose solutions alone. The results demonstrated that the carbopol/methyl cellulose mixture can be used as an in situ gelling vehicle to enhance the ocular bioavailability of pefloxacin mesylate.
Oral controlled release microspheres of rifampicin (RIF) were prepared in order to circumvent the... more Oral controlled release microspheres of rifampicin (RIF) were prepared in order to circumvent the required regular high dose of the conventional dosage forms for the treatment of tuberculosis. Rifampicin containing microspheres were designed by using a biodegradable and biocompatible polymer, gelatin B, using a thermal gelation method. The microspheres were cross-linked with natural cross-linker, sucrose, to avoid the toxicities due to the synthetic di- and poly-aldehydes. This formulation was found to be controlled release for drug in the gastro-intestinal tract. Drug encapsulation efficiency was found to be in the range of 52-83%. These microspheres were characterized for; particle size analysis by optical microscopy and scanning electron microscopy; in vitro release study by USP paddle apparatus and drug polymer interaction study using DSC and FT-IR. The results suggested that microspheres prepared by the above method were smaller in size, i.e. less than 60 microm and sucrose could be used as an interesting means to cross-link gelatin B microspheres, allowing the use of this formulation for controlled release of rifampicin. Microspheres could be observed in the intestinal lumen at 4 h and were detectable in the intestine 24 h post-oral administration, although the percentage of radioactivity had significantly decreased (t(1/2) of (99m)Tc = 4-5 h). Dissolution and scintigraphy studies have shown promising results, proving the utility of the formulation for the whole intestine.
The aim of the present study was to develop nanoemulsion as a possible vehicle for enhanced trans... more The aim of the present study was to develop nanoemulsion as a possible vehicle for enhanced transdermal penetration of carvedilol (CVD). For screening of nanoemulsion components, solubility of CVD in oils, surfactants and co-surfactants was determined. Various surfactants and co-surfactants were screened for their ability to nanoemulsify the selected oily phases. The obtained results indicated that Acconon CC6 Õ had shown good nanoemulsification efficiency (minimum surfactant required S min ¼ 46.52% w/w) among the selected surfactants and further improved in presence of CO-20 Õ (S min ¼ 37.11% w/w). The ranges of nanoemulsion existence were delineated through the construction of the pseudo-ternary phase diagram at different ratio of surfactant mixture (S/ CoS), and various nanoemulsions were selected from phase diagram of S/CoS ratio 1 : 1. The effect of content of oil and S/CoS (1 : 1) on the skin permeation of CVD was evaluated through an excised wistar rat skin using Franz diffusion cell. All the nanoemulsions showed a high skin permeation rate (92.251-161.53 mg/ cm 2 /h), good enhancement ratio (3.5-6.2) and high permeability coefficient in comparison to control groups. The optimised nanoemulsion formulation with the highest skin permeation rate (161.53 mg/cm 2 /h) consisted of 0.25% w/w CVD, 12.5% w/w Miglyol 810 Õ , 50% w/w Acconon CC6 Õ /CO-20 Õ (1 : 1) and water. The above formulation had the smallest mean globules size (9.28 nm). The superior transdermal flux of CVD may be due to nanorange size of oil globules that lead to intimate contact with the skin layer. These studies suggest that the nanoemulsion system is a promising vehicle for the transdermal delivery of CVD.
Isoniazid (INH) is the first line anti-tubercular drug that is widely used in the treatment of tu... more Isoniazid (INH) is the first line anti-tubercular drug that is widely used in the treatment of tuberculosis. (99m)Tc-alginate-INH microsphere scintigraphy has been demonstrated to be a useful noninvasive imaging technique for microsphere deposits located in different organs of the rabbits. The aim of this study was to develop an improved formulation, to validate the formulation for long-time retention, as well as to assess radiotracer stability by novel quality control methods. Our study reports the labeling and evaluation of alginate blends-INH microspheres. The incorporation efficiency of optimized formulation was 89% w/w. The in vitro release study was carried out in simulated intestinal fluid at pH 7.4, and it was found that the formulation delivered the drug for 36 h. The labeling efficiency of (99m)Tc-alginate blends-INH microspheres was seen at various pH (i.e. pH ranging from 5 to 7.5) and different concentration of stannous chloride dehydrate (i.e. 25-200 microg) and it was concluded that 96% labeling efficiency was achieved in case of pH 7.5 and 60 microg stannous chloride. The stability study was carried out in saline and serum and it was found that the complex was highly stable in vitro and in vivo. The blood clearance in rabbits showed bi-exponential pattern depicting that 50% of activity washed out at 2 h with t(1/2(Fast)) was 2.1 h and t(1/2(Slow)) was 12.5 h. Bio-distribution was normal and the experimental mice showed major accumulation of the radiolabeled formulation in liver, intestine, lungs and kidneys, indicating hepatobiliary and renal route of excretion. The distribution of the drugs to the lung was showing its efficiency in the treatment of tuberculosis.
Matrix type transdermal therapeutic systems (TTS) of glibenclamide were formulated using polymers... more Matrix type transdermal therapeutic systems (TTS) of glibenclamide were formulated using polymers Eudragit RL 100, ethyl cellulose, PVP K-30, and polyvinyl acetate, and citral was used as the penetration enhancer. The polymer fi lms were formulated with Eudragit RL 100 and PVP K-30 in different ratios and subsequently subjected to ex vivo studies (drug permeation through rat skin) followed by interaction studies, skin irritation studies, accelerated stability analysis, and in vivo studies (determination of blood glucose level in rabbits). The drug content of the formulations was found to be 99.1-99.2%. The cumulative percentages of drug permeated through rat skin from the three selected formulations in 48 h were 95.3%, 98.8%, and 99%, respectively. A plot between cumulative percent of drug permeated and square root of time exhibited linear curves, which suggests the Higuchian matrix mechanism of drug release. The formulation containing Eudragit RL 100 and PVP K-30 showed better improvement in hypoglycemic activity in rabbits (56.2-60.8% reduction in blood glucose level, p < 0.05). There were fewer fluctuations in blood glucose level as compared to oral therapy due to controlled release of the active pharmaceutical ingredient, and no interaction was found between the drug and excipients of the formulation. Accelerated stability analysis showed that the formulation was stable up to 5.5 years, with negligible skin irritation. The formulation precluded severe hypoglycemic reactions (side effect of sulfonylureas) and was effective for management of diabetes mellitus up to 48 h, with a single TTS.
The degradation of aspirin (ASA) was investigated to reveal information about the influence of co... more The degradation of aspirin (ASA) was investigated to reveal information about the influence of complexation with fulvic acid (FA), as a new complexing agent and compared with hydroxy propyl-beta-cyclodextrin complex. ASA was complexed with FA in the molar ratio 1:0.5, 1:1, and 1:2 by different methods through lyophilization, solvent evaporation, and spray drying. Spray-dried (1:1) ASA-hydroxy propyl-beta-cyclodextrin complex was prepared and compared with optimized complex of FA. All the complexes and ASA alone were packaged in well-labeled sealed polythene-lined aluminum pouches and stored in stability chamber at 40 +/- 2 degrees C and 75 +/- 5% relative humidity for 120 days. Samples were analyzed for salicylic acid content at 0, 30, 60, 90, and 120 days. Overall 4.31% salicylic acid was formed in 1:1 ASA-FA spray-dried complex, which was optimized stable complex among other complexes of FA prepared by different methods in different molar ratios. However, 2.35% salicylic acid was measured with 1:1 spray-dried ASA-hydroxy propyl-beta-cyclodextrin complex. Stability of ASA increased more when complexed with hydroxy propyl-beta-cyclodextrin as compared to FA. A novel complexing agent in the form of FA was investigated to increase the stability of ASA. A marked improvement in stability of ASA was observed when complexed with hydroxy propyl-beta-cyclodextrin (1:1) by spray drying as compared to 1:1 spray-dried ASA-FA complex.
Chitosan phthalate polymer was synthesized and its microspheres were prepared by emulsion phase s... more Chitosan phthalate polymer was synthesized and its microspheres were prepared by emulsion phase separation technique. The characterization of microspheres was determined by means of FTIR spectroscopy, electron microscopy, particle size, and zeta potential. The insulin was loaded to the microspheres by passive absorption technique. The peptic and tryptic enzymes degradation of insulin in microspheres was investigated. The in vitro release behavior of the microspheres was investigated under different pH conditions (pH 2.0 and pH 7.4). The degree of phthalate substitution in the synthesized polymer was 20%. The prepared microspheres were spherical with an average diameter 46.34 micro m. The insulin-loading capacity was 62%. Chitosan phthalate microspheres protect the insulin from gastric enzymes degradation that may enhance the oral stability of insulin. The encapsulated insulin was quickly released in a phosphate buffer saline (pH 7.4), whereas a small amount of insulin was released under acidic condition (0.1N HCl; pH 2.0) because under acidic conditions, carboxylic groups present in the system exist in nonionized form and are poorly hydrophilic. However, in alkaline conditions, it exists in ionized form and is considerably hydrophilic. The results suggest that chitosan phthalate microspheres may be used as a potential carrier for oral insulin delivery.
Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia caused by d... more Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia caused by defective insulin secretion, resistance to insulin action, or a combination of both. DM has reached epidemic proportions in the US and more recently worldwide. The morbidity and mortality associated with diabetes is anticipated to account for a substantial proportion of health care expenditures. Although there are several drug treatments currently available, the need for new herbal agents for treatment of diabetes are required. The treatment goals for patients with diabetes have evolved significantly over the last 80 years, from preventing imminent mortality, to alleviating symptoms, to the now recognized objective of normalization or near normalization of glucose levels with the intent of forestalling diabetic complications. The present review stated several findings from an extensive literature search of natural plants that have been assessed for the anti diabetic activity over past 80 years. An attempt has been made to summarize the information in order to highlight those chemical entities and plant species which are of worthy for further investigation as leads to the drug developments. Over 100 plant species from wide range of families containing various chemical classes of compounds have been cited here which are worthy for the researchers and the industrialist concerned to diabetes.
Methods and Findings in Experimental and Clinical Pharmacology, 2008
The aim of this study was to investigate and evaluate a microemulsion gel-based system of babchi ... more The aim of this study was to investigate and evaluate a microemulsion gel-based system of babchi oil (Psoralea corylifolia) for the treatment of psoriasis, which could provide improved permeation of the drug through the skin and increased patient compliance. Babchi oil is used because its chief constituent psoralen is a photoactive furocoumarin that binds to DNA when exposed to UV light to form photoproducts with pyrimidine base. This action inhibits DNA synthesis and causes decrease in cell proliferation. Moreover, babchi oil, in addition to providing psoralen, also acts as an oily phase for microemulsion system. The presence of surfactant and cosurfactant increases the permeation. On the basis of qualitative and quantitative estimation of all eight brands of babchi oil, Bakuchi Tail was selected for microemulsion formulation. Microemulsions were prepared by aqueous phase-titration method. Pseudoternary phase diagrams were constructed for the identification of microemulsion existence zones. Prepared microemulsions were subjected to different thermodynamic stability tests and characterized for droplet size, viscosity and refractive index. In vitro skin permeation of babchi oil through rat abdominal skin was determined by the Franz diffusion cell. The in vitro skin permeation profile of formulation F2, which consisted of 1.67% v/v of babchi oil, 8.33% v/v of oleic acid, S(mix) 55% v/v of Tween 80 Transcutol-P (S/Co ratio 1:1) and 35% v/v of distilled water, was significant when compared with other microemulsion formulations (p &amp;amp;amp;amp;lt; 0.05). Formulation F2 was converted into microemulsion gel by adding 1% Carbopol-940 and coded as MGF2. Formulation MGF2 was selected for its in vivo antiinflammatory effects determined by footpad edema. The results suggested that microemulsion gel is a potential vehicle for improved topical delivery of psoralen and that microemulsion gels are potential vehicles for improved topical delivery of babchi oil.
A quantitative method using precoated silica gel-60 Lichrosphere highperformance thin-layer chrom... more A quantitative method using precoated silica gel-60 Lichrosphere highperformance thin-layer chromatography (HPTLC) plates, automated band wise sample application, and n-hexane:acetone:formic acid (2:1:0.025 v/v/v) as mobile phase, has been developed and validated for the analysis of psoralen in marketed formulations and novel solid lipid nanoparticles (SLNs). Densitometric analysis was performed at 250 nm in absorbance mode. Compact bands of psoralen were obtained at R f 0.32 ± 0.02. The method was validated for linearity, precision, robustness, sensitivity, specificity, and recovery. Linearity (r 2 = 0.995), limit of detection (8.0 ng band −1), limit of quantification (18.1 ng band −1), recovery (98.06-99.64%), and precision (≤0.74) were satisfactory. Statistical analysis established that the developed method for quantification of psoralen in marketed formulation and from solid lipid nanoparticles is reproducible and selective.
A simple, selective, precise, accurate, and cost-effective thin-layer chromatographic (TLC) metho... more A simple, selective, precise, accurate, and cost-effective thin-layer chromatographic (TLC) method for analysis of psoralen in different brands of babchi (Psoralea corylifolia) oil has been developed and validated. Aluminium TLC plates precoated with silica gel 60F 254 were used as the stationary phase and n-hexane-acetone-formic acid 2:1:0.025 (v/v) as mobile phase. A compact, resolved psoralen peak (R F value 0.32 ± 0.02) was observed by densitometric analysis in absorbance mode at 250 nm. Calibration data revealed a good linear relationship (r 2 = 0.9956) between peak area and concentration in the range 20-200 ng per spot. Mean ± SD values of slope and intercept were 11.35 ± 0.36 and 14.64 ± 0.31, respectively. Statistical analysis proved the method to be a repeatable, selective, and accurate means of estimation of psoralen in different brands of babchi oil.
Our knowledge in the field of ocular drug delivery is rapidly expanding. An increase in the under... more Our knowledge in the field of ocular drug delivery is rapidly expanding. An increase in the understanding of ocular drug absorption and disposition vis-à-vis developments in nanotechnology has led to the emergence of many of the nanotechnology-based ocular drug delivery systems including nanoparticles, microemulsions, liposomes, solid lipid nanoparticles, light-sensitive nanocarrier systems, etc. The need to develop effective treatments for posterior eye segment diseases is more important than surface delivery. Treatment of blinding diseases of the eye, such as proliferative retinopathy or macular degeneration, requires effective and safe delivery of drugs to posterior eye segment tissues, and recent advances in nanotechnology have demonstrated successful outcomes. Nanoscientists should focus their efforts on nano-ophthalmology. This review describes the current status and progress made so far, and the course that needs to be pursued in the future.
In the present study, spherical microspheres able to prolong the release of INH were produced by ... more In the present study, spherical microspheres able to prolong the release of INH were produced by a modified emulsification method, using sodium alginate as the hydrophilic carrier. The shape and surface characteristics were determined by scanning electron microscopy using gold sputter technique. Particle sizes of both placebo and drug-loaded formulations were measured by SEM and the particle size distribution was determined by an optical microscope. The physical state of the drug in the formulation was determined by differential scanning calorimetry (DSC). The release profiles of INH from microspheres were examined in simulated gastric fluid (SGF pH 1.2) and simulated intestinal fluid (SIF pH 7.4). Gamma-scintigraphic studies were carried out to determine the location of microspheres on oral administration and the extent of transit through the gastrointestinal tract (GIT). The microspheres had a smoother surface and were found to be discreet and spherical in shape. The particles were heterogeneous with the maximum particles of an average size of 3.719 m. Results indicated that the mean particle size of the microspheres increased with an increase in the concentration of polymer and the cross-linker as well as the cross-linking time. The entrapment efficiency was found to be in the range of 40-91%. Concentration of the cross-linker up to 7.5% caused increase in the entrapment efficiency and the extent of drug release. Optimized isoniazid-alginate microspheres were found to possess good bioadhesion (72.25 ± 1.015%). The bioadhesive property of the particles resulted in prolonged retention in the small intestine. Microspheres could be observed in the intestinal lumen at 4 h and were detectable in the intestine 24 h post-oral administration, although the percent radioactivity had significantly decreased (t 1/2 of 99m Tc = 4-5 h). Increased drug loading (91%) was observed for the optimized formulation suggesting the efficiency of the method. Nearly 26% of INH was released in SGF pH 1.2 in 6 h and 71.25% in SIF pH 7.4 in 30 h. No significant drug-polymer interactions were observed in FT-IR studies. Dissolution and ␥-scintigraphy studies have shown promising results proving the utility of the formulation for enteric drug delivery.
The objective of the present study was to investigate the effect of various terpenes, including a... more The objective of the present study was to investigate the effect of various terpenes, including a diterpene, forskolin (FSK; a putative penetration enhancer), on skin permeation of valsartan. Permeation studies were carried out with Automated Transdermal Diffusion Cells Sampling System (SFDC 6, LOGAN Instruments Corp., NJ, USA) through rat skin and human cadaver skin (HCS) using ethanol: IPB (pH 7.4) (40:60) as vehicle. The efficacy of the study terpenes for permeation of valsartan across rat skin and human cadaver skin was found in the order of cineole > d-limonene > l-menthol > linalool > FSK and cineole > d-limonene > linalool > l-menthol > FSK, respectively. No apparent skin irritation (erythema, edema) was observed on treatment of skin with terpenes including FSK. FT-IR, DSC, and histopathological studies revealed that FSK enhanced the skin permeation of the active drug by disruption and extraction of lipid bilayers of SC in consonance with other terpenes.
International journal of pharmaceutics, Jan 25, 2013
The aim of the current investigation is to develop and statistically optimize nanoethosomes for t... more The aim of the current investigation is to develop and statistically optimize nanoethosomes for transdermal valsartan delivery. Box-Behnken experimental design was applied for optimization of nanoethosomes. The Independent variables were phospholipids 90G (X(1)), ethanol (X(2)), valsartan (X(3)) and sonication Time (X(4)) while entrapment efficiency (Y(1)), vesicle size (Y(2)) and flux (Y(3)) were the dependent variables. The optimized formulation obtained was then tested in rats for an in vivo pharmacokinetic study. Results indicate that the nanoethosomes of valsartan provides better flux, reasonable entrapment efficiency, more effectiveness for transdermal delivery as compared to rigid liposomes. Optimized nanoethosomal formulation with mean particle size is 103±5.0nm showed 89.34±2.54% entrapment efficiency and achieved mean transdermal flux 801.36±21.45μg/cm(2)/hr. Nanoethosomes proved significantly superior in terms of, amount of drug permeated in the skin, with an enhancement ...
The major purpose of this study was to develop and characterize a series of carbopol- and methyl ... more The major purpose of this study was to develop and characterize a series of carbopol- and methyl cellulose-based solutions as the in situ gelling vehicles for ophthalmic drug delivery. The rheological properties, in vitro release as well as in vivo pharmacological response of a combination of polymer solutions, including carbopol and methyl cellulose, were evaluated. It was found that the optimum concentration of carbopol solution for the in situ gel-forming delivery systems was 0.3% (w/w), and that for methyl cellulose solution was 1.5% (w/w). The mixture of 0.3% carbopol and 1.5% methyl cellulose solutions showed a significant enhancement in gel strength in the physiological condition; this gel mixture was also found to be free flowing at pH 4.0 and 25 degrees C. The rheological behaviors of carbopol/methyl cellulose solution were not affected by the incorporation of the drug. Drug levels in the aqueous humor of the rabbits were well above the MIC-values of relevant bacteria after 12 hours, the results of an optimized formulation containing 0.18% of pefloxacin mesylate compared well with the 0.3% marketed eye drop formulation, indicating our formulation to be significantly better considering that a similar effect was obtained at half the concentration. Both the in vitro release and in vivo pharmacological studies indicated that the carbopol/methyl cellulose solution had better ability to retain drug than did the carbopol or methyl cellulose solutions alone. The results demonstrated that the carbopol/methyl cellulose mixture can be used as an in situ gelling vehicle to enhance the ocular bioavailability of pefloxacin mesylate.
Oral controlled release microspheres of rifampicin (RIF) were prepared in order to circumvent the... more Oral controlled release microspheres of rifampicin (RIF) were prepared in order to circumvent the required regular high dose of the conventional dosage forms for the treatment of tuberculosis. Rifampicin containing microspheres were designed by using a biodegradable and biocompatible polymer, gelatin B, using a thermal gelation method. The microspheres were cross-linked with natural cross-linker, sucrose, to avoid the toxicities due to the synthetic di- and poly-aldehydes. This formulation was found to be controlled release for drug in the gastro-intestinal tract. Drug encapsulation efficiency was found to be in the range of 52-83%. These microspheres were characterized for; particle size analysis by optical microscopy and scanning electron microscopy; in vitro release study by USP paddle apparatus and drug polymer interaction study using DSC and FT-IR. The results suggested that microspheres prepared by the above method were smaller in size, i.e. less than 60 microm and sucrose could be used as an interesting means to cross-link gelatin B microspheres, allowing the use of this formulation for controlled release of rifampicin. Microspheres could be observed in the intestinal lumen at 4 h and were detectable in the intestine 24 h post-oral administration, although the percentage of radioactivity had significantly decreased (t(1/2) of (99m)Tc = 4-5 h). Dissolution and scintigraphy studies have shown promising results, proving the utility of the formulation for the whole intestine.
The aim of the present study was to develop nanoemulsion as a possible vehicle for enhanced trans... more The aim of the present study was to develop nanoemulsion as a possible vehicle for enhanced transdermal penetration of carvedilol (CVD). For screening of nanoemulsion components, solubility of CVD in oils, surfactants and co-surfactants was determined. Various surfactants and co-surfactants were screened for their ability to nanoemulsify the selected oily phases. The obtained results indicated that Acconon CC6 Õ had shown good nanoemulsification efficiency (minimum surfactant required S min ¼ 46.52% w/w) among the selected surfactants and further improved in presence of CO-20 Õ (S min ¼ 37.11% w/w). The ranges of nanoemulsion existence were delineated through the construction of the pseudo-ternary phase diagram at different ratio of surfactant mixture (S/ CoS), and various nanoemulsions were selected from phase diagram of S/CoS ratio 1 : 1. The effect of content of oil and S/CoS (1 : 1) on the skin permeation of CVD was evaluated through an excised wistar rat skin using Franz diffusion cell. All the nanoemulsions showed a high skin permeation rate (92.251-161.53 mg/ cm 2 /h), good enhancement ratio (3.5-6.2) and high permeability coefficient in comparison to control groups. The optimised nanoemulsion formulation with the highest skin permeation rate (161.53 mg/cm 2 /h) consisted of 0.25% w/w CVD, 12.5% w/w Miglyol 810 Õ , 50% w/w Acconon CC6 Õ /CO-20 Õ (1 : 1) and water. The above formulation had the smallest mean globules size (9.28 nm). The superior transdermal flux of CVD may be due to nanorange size of oil globules that lead to intimate contact with the skin layer. These studies suggest that the nanoemulsion system is a promising vehicle for the transdermal delivery of CVD.
Isoniazid (INH) is the first line anti-tubercular drug that is widely used in the treatment of tu... more Isoniazid (INH) is the first line anti-tubercular drug that is widely used in the treatment of tuberculosis. (99m)Tc-alginate-INH microsphere scintigraphy has been demonstrated to be a useful noninvasive imaging technique for microsphere deposits located in different organs of the rabbits. The aim of this study was to develop an improved formulation, to validate the formulation for long-time retention, as well as to assess radiotracer stability by novel quality control methods. Our study reports the labeling and evaluation of alginate blends-INH microspheres. The incorporation efficiency of optimized formulation was 89% w/w. The in vitro release study was carried out in simulated intestinal fluid at pH 7.4, and it was found that the formulation delivered the drug for 36 h. The labeling efficiency of (99m)Tc-alginate blends-INH microspheres was seen at various pH (i.e. pH ranging from 5 to 7.5) and different concentration of stannous chloride dehydrate (i.e. 25-200 microg) and it was concluded that 96% labeling efficiency was achieved in case of pH 7.5 and 60 microg stannous chloride. The stability study was carried out in saline and serum and it was found that the complex was highly stable in vitro and in vivo. The blood clearance in rabbits showed bi-exponential pattern depicting that 50% of activity washed out at 2 h with t(1/2(Fast)) was 2.1 h and t(1/2(Slow)) was 12.5 h. Bio-distribution was normal and the experimental mice showed major accumulation of the radiolabeled formulation in liver, intestine, lungs and kidneys, indicating hepatobiliary and renal route of excretion. The distribution of the drugs to the lung was showing its efficiency in the treatment of tuberculosis.
Matrix type transdermal therapeutic systems (TTS) of glibenclamide were formulated using polymers... more Matrix type transdermal therapeutic systems (TTS) of glibenclamide were formulated using polymers Eudragit RL 100, ethyl cellulose, PVP K-30, and polyvinyl acetate, and citral was used as the penetration enhancer. The polymer fi lms were formulated with Eudragit RL 100 and PVP K-30 in different ratios and subsequently subjected to ex vivo studies (drug permeation through rat skin) followed by interaction studies, skin irritation studies, accelerated stability analysis, and in vivo studies (determination of blood glucose level in rabbits). The drug content of the formulations was found to be 99.1-99.2%. The cumulative percentages of drug permeated through rat skin from the three selected formulations in 48 h were 95.3%, 98.8%, and 99%, respectively. A plot between cumulative percent of drug permeated and square root of time exhibited linear curves, which suggests the Higuchian matrix mechanism of drug release. The formulation containing Eudragit RL 100 and PVP K-30 showed better improvement in hypoglycemic activity in rabbits (56.2-60.8% reduction in blood glucose level, p < 0.05). There were fewer fluctuations in blood glucose level as compared to oral therapy due to controlled release of the active pharmaceutical ingredient, and no interaction was found between the drug and excipients of the formulation. Accelerated stability analysis showed that the formulation was stable up to 5.5 years, with negligible skin irritation. The formulation precluded severe hypoglycemic reactions (side effect of sulfonylureas) and was effective for management of diabetes mellitus up to 48 h, with a single TTS.
The degradation of aspirin (ASA) was investigated to reveal information about the influence of co... more The degradation of aspirin (ASA) was investigated to reveal information about the influence of complexation with fulvic acid (FA), as a new complexing agent and compared with hydroxy propyl-beta-cyclodextrin complex. ASA was complexed with FA in the molar ratio 1:0.5, 1:1, and 1:2 by different methods through lyophilization, solvent evaporation, and spray drying. Spray-dried (1:1) ASA-hydroxy propyl-beta-cyclodextrin complex was prepared and compared with optimized complex of FA. All the complexes and ASA alone were packaged in well-labeled sealed polythene-lined aluminum pouches and stored in stability chamber at 40 +/- 2 degrees C and 75 +/- 5% relative humidity for 120 days. Samples were analyzed for salicylic acid content at 0, 30, 60, 90, and 120 days. Overall 4.31% salicylic acid was formed in 1:1 ASA-FA spray-dried complex, which was optimized stable complex among other complexes of FA prepared by different methods in different molar ratios. However, 2.35% salicylic acid was measured with 1:1 spray-dried ASA-hydroxy propyl-beta-cyclodextrin complex. Stability of ASA increased more when complexed with hydroxy propyl-beta-cyclodextrin as compared to FA. A novel complexing agent in the form of FA was investigated to increase the stability of ASA. A marked improvement in stability of ASA was observed when complexed with hydroxy propyl-beta-cyclodextrin (1:1) by spray drying as compared to 1:1 spray-dried ASA-FA complex.
Chitosan phthalate polymer was synthesized and its microspheres were prepared by emulsion phase s... more Chitosan phthalate polymer was synthesized and its microspheres were prepared by emulsion phase separation technique. The characterization of microspheres was determined by means of FTIR spectroscopy, electron microscopy, particle size, and zeta potential. The insulin was loaded to the microspheres by passive absorption technique. The peptic and tryptic enzymes degradation of insulin in microspheres was investigated. The in vitro release behavior of the microspheres was investigated under different pH conditions (pH 2.0 and pH 7.4). The degree of phthalate substitution in the synthesized polymer was 20%. The prepared microspheres were spherical with an average diameter 46.34 micro m. The insulin-loading capacity was 62%. Chitosan phthalate microspheres protect the insulin from gastric enzymes degradation that may enhance the oral stability of insulin. The encapsulated insulin was quickly released in a phosphate buffer saline (pH 7.4), whereas a small amount of insulin was released under acidic condition (0.1N HCl; pH 2.0) because under acidic conditions, carboxylic groups present in the system exist in nonionized form and are poorly hydrophilic. However, in alkaline conditions, it exists in ionized form and is considerably hydrophilic. The results suggest that chitosan phthalate microspheres may be used as a potential carrier for oral insulin delivery.
Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia caused by d... more Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia caused by defective insulin secretion, resistance to insulin action, or a combination of both. DM has reached epidemic proportions in the US and more recently worldwide. The morbidity and mortality associated with diabetes is anticipated to account for a substantial proportion of health care expenditures. Although there are several drug treatments currently available, the need for new herbal agents for treatment of diabetes are required. The treatment goals for patients with diabetes have evolved significantly over the last 80 years, from preventing imminent mortality, to alleviating symptoms, to the now recognized objective of normalization or near normalization of glucose levels with the intent of forestalling diabetic complications. The present review stated several findings from an extensive literature search of natural plants that have been assessed for the anti diabetic activity over past 80 years. An attempt has been made to summarize the information in order to highlight those chemical entities and plant species which are of worthy for further investigation as leads to the drug developments. Over 100 plant species from wide range of families containing various chemical classes of compounds have been cited here which are worthy for the researchers and the industrialist concerned to diabetes.
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Papers by Y. Sultana