Mohd Yasir

Status of surfactants as penetration enhancers in transdermal drug delivery

Surfactants are found in many existing therapeutic, cosmetic, and agro-chemical preparations. In recent years, surfactants have been employed to enhance the permeation rates of several drugs via transdermal route. The application of transdermal route to a wider range of drugs is limited due to significant barrier to penetration across the skin which is associated with the outermost stratum corneum layer. Surfactants have effects on the permeability characteristics of several biological membranes including skin. They have the potential to solubilize lipids within the stratum corneum. The penetration of the surfactant molecule into the lipid lamellae of the stratum corneum is strongly dependent on the partitioning behavior and solubility of surfactant. Surfactants ranging from hydrophobic agents such as oleic acid to hydrophilic sodium lauryl sulfate have been tested as permeation enhancer to improve drug delivery. This article reviews the status of surfactants as permeation enhancer in transdermal drug delivery of various drugs.

Solid lipid nanoparticles for nose to brain delivery of haloperidol: in vitro drug release and pharmacokinetics evaluation

In the present study, haloperidol (HP)-loaded solid lipid nanoparticles (SLNs) were prepared to enhance the uptake of HP to brain via intranasal (i.n.) delivery. SLNs were prepared by a modified emulsification–diffusion technique and evaluated for particle size, zeta potential, drug entrapment efficiency, in vitro drug release, and stability. All parameters were found to be in an acceptable range. In vitro drug release was found to be 94.16±4.78% after 24 h and was fitted to the Higuchi model with a very high correlation coefficient (R2=0.9941). Pharmacokinetics studies were performed on albino Wistar rats and the concentration of HP in brain and blood was measured by high performance liquid chromatography. The brain/blood ratio at 0.5 h for HP-SLNs i.n., HP sol. i.n. and HP sol. i.v. was 1.61, 0.17 and 0.031, respectively, indicating direct nose-to-brain transport, bypassing the blood–brain barrier. The maximum concentration (Cmax) in brain achieved from i.n. administration of HP-SLNs (329.17±20.89 ng/mL, Tmax 2 h) was significantly higher than that achieved after i.v. (76.95±7.62 ng/mL, Tmax 1 h), and i.n. (90.13±6.28 ng/mL, Tmax 2 h) administration of HP sol. The highest drug-targeting efficiency (2362.43%) and direct transport percentage (95.77%) was found with HP-SLNs as compared to the other formulations. Higher DTE (%) and DTP (%) suggest that HP-SLNs have better brain targeting efficiency as compared to other formulations.

Haloperidol Loaded Solid Lipid Nanoparticles for Nose to Brain Delivery:Stability and In vivo Studies

In the present study, Haloperidol loaded solid lipid nanoparticles were prepared to enhance its uptake to brain via intranasal route. SLNs were prepared by modified emulsification diffusion technique. For optimization, a three factors and three levels Box - Behnken design was applied to study the effect of independent variables (factors) i.e. drug to lipid ratio (A), surfactant concentration (B) and stirring speed (C) on dependent variables (responses) i.e. particles size (Y1), entrapment efficiency (Y2), and drug loading (Y3). The value of optimized variables for HP-SLNs was 1:2 (drug to lipid ratio), 1.625% (surfactant concentration) and 3000 rpm (stirring speed). The optimized HP-SLNs formulation was evaluated for stability and in vivo studies. Stability studies revealed no significant (P<0.5) change was observed in particle size, zeta potential, entrapment efficiency and drug loading of optimized HP-SLNs formulation when it was stored at 4 ± 2°C (refrigerator) and 25 ± 2°C/60 ± 5% RH up to six months, but the size of particles was increased significantly (P<0.001) when the optimized formulation was stored at 40 ± 2°C/75 ± 5% RH. A significant drop (P<0.001) in zeta potential was also observed at 40 ± 2°C/75 ± 5% RH after 3 months. In vivo studies were performed on albino Wistar rats and various pharmacokinetic and brain targeting parameters were determined. The pharmacokinetic parameters in brain after i.n. administration of HP-SLNs were found to be, Tmax 2 h, Cmax 329.17 ± 20.89 ng/mL, AUC0 - ∞ 2389.17 ± 78.82 ng.h/mL, Ke 0.079 ± 0.0065 h-1 and MRT 12.60 ± 0.99 h. The value of brain targeting parameters like drug targeting index, drug targeting efficiency and nose to brain direct transport were found to be 23.62, 2362.43% and 95.77% and 11.28, 1128.61% and 91.14% for HP-SLNs i.n. and HP Sol i.n. respectively.

Development and Validation of UV Spectrophotometric Method for the Estimation of Haloperidol.

Aims: The aim of the present work was to develop and validate a sensitive, simple, accurate, precise & cost effective UV spectrophotometric method for the estimation of haloperidol in prepared pharmaceutical formulations of solid lipid nanoparticles. Methodology: The different analytical performance parameters such as linearity, range, precision, accuracy, limit of detection (LOD) and limit of quantification (LOQ) were determined according to International Conference on Harmonization (ICH) Q2 (R1) guidelines. The study was performed in phosphate buffer of pH 7.4. Results: The peak (λmax) of haloperidol appeared at a wavelength of 247.5 nm in phosphate buffer (pH 7.4). Beer-Lambert’s law was obeyed in the concentration range of 2–20 μg/ml with correlation coefficient (R) 0.9994. Conclusion: The results of the study demonstrated that the developed procedure was accurate, precise and reproducible, while being simple, cheap and less time consuming. Original Research Article British Journal of Pharmaceutical Research, 4(11): 1407-1415, 2014 1408 Therefore, this method can be suitably applied for the estimation of haloperidol in prepared solid lipid nanoparticles.

Solid Lipid Nanoparticles Approach for Lymphatic Targeting Through Intraduodenal Delivery of Quetiapine Fumarate

BACKGROUND Lymphatic route is one of the prominent routes for improving the poor bioavailability of the drugs which undergo extensive hepatic first pass metabolism. Nanocarriers (solid lipid nanoparticles) offer a new drug delivery system that could hold great promise for attaining the bioavailability enhancement along with controlled and site specific drug delivery. OBJECTIVE The aim of the present research work was to prepare and optimized the Quetiapine fumarate (an antipsychotic drug) loaded solid lipid nanoparticles for lymphatic targeting through intraduodenal administration. METHOD Thirteen quetiapine fumarate loaded solid lipid nanoparticle formulations were developed using different lipids by Microemulsion technique and optimized by box behnken design. RESULTS Optimized formulation (Q9) had a mean particle size of 230.38 nm with 75.92% of entrapment efficiency. The percentage drug release after 24 h was found to be 95.81%. A significant difference (P<0.05) was found in the in vitro release data of optimized formulation as compared to marketed formulation. In vitro release data of optimized formulation (Q9) was subjected to zero order, first order and Higuchi model to evaluate the release kinetics. Higuchi model was found to be the best fitted model with highest value of correlation coefficient (R2= 0.999). In vivo studies for optimized solid lipid nanoparticles formulation and drug suspension were performed on male Wistar rats after intraduodenal administration and several pharmacokinetic parameters were determined. AUC (0-∞) of optimized formulation was significantly (P<0.01) more than that of drug suspension. Bioavailability of quetiapine in solid lipid nanoparticles was 2.76 fold increased after intraduodenal administration as compared with that of drug suspension. CONCLUSION On the basis of results of in vitro study, Q9 formulation was selected as optimized formulation. It exhibited better bioavailability as compared to drug suspension. It can be concluded that solid lipid nanoparticles are potential carrier for improving quetiapine bioavailability through lymphatic delivery.

Solid lipid nanoparticles for nose to brain delivery of donepezil: formulation, optimization by Box–Behnken design, in vitro and in vivo evaluation

Abstract This study was aimed at preparing and characterizing solid lipid nanoparticles (SLNs) of donepezil (DPL) for delivery to brain via nasal route. SLNs were prepared by solvent emulsification diffusion technique using glyceryl monostearate (GMS) as lipid and blend of tween 80 and poloxamer 188 (1:1) as surfactant. Box–Behnken design was applied for optimization by using drug to lipid ratio, surfactant concentration and stirring time as dependent variables and their effect were observed on particles size, entrapment efficiency and drug loading. Optimized formulation was evaluated for particle size, zeta potential, entrapment efficiency, drug loading, morphological analysis, crystallinity, in vitro drug release, in vivo (biodistribution, pharmacokinetic and Gama scintigraphy) studies. For optimized formulation (OD3), value of particle size, zeta potential, percent in vitro release, entrapment efficiency and drug loading was found to be 121.0 nm, –24.1 mV, 89.35%, 67.95% and 12.15%, respectively. Pharmacokinetic and biodistribution studies were performed on albino Wistar rats and value of AUC0–∞ in brain for DPL-SLNs i.n. was found to be nearly 2.61 times higher than that of DPL-Sol i.v., whereas 2.26 times superior than DPL-Sol administered intranasally. The scintigraphy images were taken in rabbit and result revealed the localization of drug in brain.

Formulation and Evaluation of Glyceryl Behenate based Solid Lipid Nanoparticles for the Delivery of Donepezil to Brain through Nasal Route

In the present study, Donepezil (DPL) loaded solid lipid nanoparticles (SLNs) were formulated for brain targeting through nasal route. SLNs were prepared by solvent emulsification diffusion technique using Glyceryl behenate as lipid and blend of tween 80 and poloxamer 188 (1:1) as surfactant. SLNs were evaluated for particle size, zeta potential, drug entrapment efficiency, In vitro drug release, stability and in vivo studies. For optimized formulation, in vitro drug release was found to be 96.72 ± 5.89% in 24 h and Higuchi model was found to be fitted with highest value of correlation coefficient (R2= 0.9504). Stability studies revealed no significant (P< 0.5) change in particle size, zeta potential, entrapment efficiency and drug loading of optimized DPL-SLNs formulation when it was stored at 4±2 °C (refrigerator) and 25±2 °C /60 ±5% RH up to six months, but the size of particles was increased significantly (P?0.001) when the optimized formulation was stored at 40±2 °C /75±5% RH. In vivo studies were performed on albino wistar rats and various pharmacokinetic and brain targeting parameters were determined. The value of AUC 0-8 in brain for DPL-SLNs i.n. was found to be nearly 1.97 times higher than that of DPL-Sol. i.v., whereas 1.63 times superior than DPL-Sol. administered intranasally. The higher drug targeting efficiency (288.75%) and direct transport percentage (65.37%) with optimized formulation indicates better brain targeting efficiency as compared to other formulations.

ANTIFUNGAL ACTIVITY OF AQUEOUS AND HYDROALCOHOLIC EXTRACTS OF DESERT PLANT DHAMASA AND THEIR COMPARISON BY STATISTICAL ANALYSIS

Herbal plant Dhamasa is widely distributed in deserts and dry areas of India, Pakistan to tropical Africa. Botanical name of Dhamasa is Fagonia schweinfurthii Hadidi (Family-Zygophyllaceae). Traditionally it is boiled in water and its bath is taken for allergies and other skin diseases. In this study the antifungal activity of the aqueous and hydroalcoholic extracts of Dhamasa were evaluated. Aqueous extract was prepared by decoction method and hydroalcoholic extract was prepared by soxhletion method. The evaluation of antifungal activity of plant extracts was determined as the minimum inhibitory concentration (MIC) followed by cup plate method against three fungal strains. Inherent antifungal activity of aqueous as well as hydro-alcoholic extract of Dhamasa was found. For the comparison of results Student’s t test was applied on the values of diameters of zones of inhibitions produced by aqueous and hydroalcoholic extracts. The result indicated that aqueous as fungal strains. Statistical analysis of results reveal that there was no significant difference in the antifungal potential of aqueous as well as hydroalcoholic extract possess almost equal antifungal potential against selected. These extract can be used in various antifungal topical preparations.

Development and Validation of a New HPLC Method for In-vitro Studies of Haloperidol in Solid Lipid Nanoparticles

A simple and sensitive HPLC method was developed and validated for the study of in-vitro drug release from haloperidol loaded solid lipid nanoparticles (SLNs). The method was also used for the analysis of drug for detection of shelf life of developed SLNs. Chromatogram separation was achieved using C18 column as stationary phase. The mobile phase consisted of 100 mM/L potassium dihydrogen phosphate–acetonitrile-TEA (10:90:0.1, v/v/v) and the pH was adjusted with o-phosphoric acid to 3.5. Flow rate of mobile phase was 2 ml/minute and eluents were monitored at 230 nm using UV/VIS detector. The method was validated for linearity, precision, accuracy, reproducibility, limit of detection (LOD) and limit of quantification (LOQ). Linearity for haloperidol was in the range of 1-60 μg/mL. The value of LOD and LOQ was found to be 0.045 and 0.135 μg/ml respectively. The drug loaded SLNs showed sustained drug release with maximum value of 95.52 ± 5.21% in 24 h. The shelf life of SLNs formulation was found to be 2.31 years at 4°C.