Syed Sarim Imam

Application of Box–Behnken design for preparation of levofloxacin-loaded stearic acid solid lipid nanoparticles for ocular delivery: Optimization, in vitro release, ocular tolerance, and antibacterial activity

The aim of the present study was to develop and optimize levofloxacin loaded solid lipid nanoparticles for the treatment of conjunctivitis. Box-Behnken experimental design was applied for optimization of solid lipid nanoparticles. The independent variables were stearic acid as lipid (X1), Tween 80 as surfactant (X2) and sodium deoxycholate as co-surfactant (X3) while particle size (Y1) and entrapment efficiency (Y2) were the dependent variables. Further in vitro release and antibacterial activity in vitro were also performed. The optimized formulation of levofloxacin provides particle size of 237.82 nm and showed 78.71% entrapment efficiency and achieved flux 0.2,493 μg/cm(2)/h across excised goat cornea. In vitro release study showed prolonged drug release from the optimized formulation following Korsmeyer-Peppas model. Antimicrobial study revealed that the developed formulation possesses antibacterial activity against Staphylococcus aureus, and Escherichia coli equivalent to marketed eye drops. HET-CAM test demonstrated that optimized formulation was found to be non-irritant and safe for topical ophthalmic use. Our results concluded that solid lipid nanoparticles are an efficient carrier for ocular delivery of levofloxacin and other drugs.

Formulation by design-based proniosome for accentuated transdermal delivery of risperidone: in vitro characterization and in vivo pharmacokinetic study

Abstract Aim: The aim of this work was to investigate the effects of formulation variables on the development of risperidone proniosomal formulations as potential transdermal delivery systems. Materials and methods: A 43 factorial design was employed to evaluate individual and combined effects of formulation variables cholesterol (X1), span 60 (X2), phospholipid G90 (X3), and risperidone (X4) added on vesicle size (Y1), encapsulation efficiency (Y2), and flux (Y3) of proniosomes. Results and discussion: The investigated risperidone-loaded proniosomal formulation shows significantly higher skin permeation in comparison to conventional liposomes with ER of 4.4 times through rat skin. The bioavailability studies in rats indicated that mean value of AUC0–48 by ROPF-TTS was 1.31 times higher than that of oral dosage form. So it could be concluded that Cmax value of ROPF-TTS was significantly reduced while AUC values were apparently increased. Conclusion: The developed proniosomal-based transdermal therapeutic systems incorporating risperidone would provide a useful strategy for better management of schizophrenia.

Formulation and optimization of niosomes for topical diacerein delivery using 3-factor, 3-level Box-Behnken design for the management of psoriasis

This research aimed towards the design of preparations of diacerein loaded cholesterol rich niosomes by employing a 3-factor, 3-level Box-Behnken design. Results indicated that Span 60 (90mg) and cholesterol (10mg), and 45min of hydration time were found to be optimum for niosomes preparation. The prepared cholesterol rich niosomes were uniform and spherical in size. Optimized formulation F2 entrapped the drug with 83.02% efficiency in the cholesterol rich niosomes of the size 477.8nm, presented the flux of 2.820μg/cm(2)/h, followed Higuchi model and non Fickian transport mechanism. The confocal laser scanning microscopy showed that niosomes accentuated the penetration of diacerein in the epidermal and dermal layer of rat skin. Stability study confirmed that cholesterol rich niosomes were stable for 2months at 4°C. Concisely, the results showed that targeted diacerein delivery might be achieved using topically applied niosomes for enhanced treatment of psoriasis, which might eliminate adverse side effects associated with systemic exposure.

Design, formulation and optimization of novel soft nano-carriers for transdermal olmesartan medoxomil delivery: In vitro characterization and in vivo pharmacokinetic assessment.

Olmesartan is a hydrophobic antihypertensive drug with a short biological half-life, and low bioavailability, presents a challenge with respect to its oral administration. The objective of the work was to formulate, optimize and evaluate the transdermal potential of novel vesicular nano-invasomes, containing above anti-hypertensive agent. To achieve the above purpose, soft carriers (viz. nano-invasomes) of olmesartan with β-citronellene as potential permeation enhancer were developed and optimized using Box-Behnken design. The physicochemical characteristics e.g., vesicle size, shape, entrapment efficiency and skin permeability of the nano-invasomes formulations were evaluated. The optimized formulation was further evaluated for in vitro drug release, confocal microscopy and in vivo pharmacokinetic study. The optimum nano-invasomes formulation showed vesicles size of 83.35±3.25nm, entrapment efficiency of 65.21±2.25% and transdermal flux of 32.78±0.703 (μg/cm(2)/h) which were found in agreement with the predicted value generated by Box-Behnken design. Confocal laser microscopy of rat skin showed that optimized formulation was eventually distributed and permeated deep into the skin. The pharmacokinetic study presented that transdermal nano-invasomes formulation showed 1.15 times improvement in bioavailability of olmesartan with respect to the control formulation in Wistar rats. It was concluded that the response surfaces estimated by Design Expert(®) illustrated obvious relationship between formulation factors and response variables and nano-invasomes were found to be a proficient carrier system for transdermal delivery of olmesartan.

DOE-Based Stability Indicating RP-HPLC Method for Determination ofLacidipine in Niosomal Gel in Rat: Pharmacokinetic Determination

Lacidipine (LAC) is a calcium channel blocker used in treatment of hypertension. In this study high performance liquid chromatography method (HPLC) is applied to the determination of LAC in rat plasma. The design of experiment used 3- factor 3- level Box Behnken Design for optimization of mobile phase condition. The effluent was monitored by UV detector at 240 nm, at a flow rate of 1.0 mL/min using amlodipine as internal standard. A linear calibration curve very well fits our data from 20-1200 ng/mL with limit of detection (LOD) quantitation (LOQ) 1.490 and 4.848 ng mL-1 respectively. The method was found to be linear, precise and accurate. Analytes were stable under various conditions (during freeze-thaw, at room temperature, and under deep freeze conditions). The pharmacokinetic study was performed after application of LAC niosomal transgel in rats and results showed enhance bioavailability by 2.57 fold as compared to oral formulation.

Nanostructured lipid carriers of pioglitazone for transdermal application: from experimental design to bioactivity detail

Abstract Pioglitazone (PZ) an anti-hyperglycemic agent is used in the treatment of type 2 diabetes. The aim of this study was to design PZ-loaded nanostructured lipid carriers (NLC) to investigate the bioavailability improvement by transdermal delivery. PZ NLCs were prepared using high-pressure homogenization followed by ultrasonication. The NLCs were evaluated for particle size analysis, drug loading, ex vivo skin transport studies and in vivo bioactivity study. The prepared NLCs had a mean size of 166.05 nm and drug loading of 10.41% with flux value of 47.36 µg/cm2/h. The entrapment of PZ is >70% in the NLCs with enhancement ratio of 3.2 times. The in vivo pharmacokinetic study showed 2.17 times enhancement in bioavailability study and pharmacodynamics study showed that PZ NLC-based transdermal therapeutic system (PNLG-TTS) lowers blood sugar level in a sustained pattern for a prolonged period of time as compared to Piosys tablet (marketed). The shelf life of the optimized formulation was found to be 1.83 years. These results clearly provide a lead that above NLCs-based TTS is potential controlled release formulation for PZ and could be a promising drug delivery system for the treatment of diabetes.

A validated RP-HPLC method for simultaneous determination of propranolol and valsartan in bulk drug and gel formulation

Objective: A simple, precise, and stability indicating high performance liquid chromatography (HPLC) method was developed and validated for the simultaneous determination of propranolol hydrochloride and valsartan in pharmaceutical dosage form. Materials and Methods: The method involves the use of easily available inexpensive laboratory reagents. The separation was achieved on Hypersil ODS C-18 column (250*4.6 mm, i.d., 5 μm particle size) with isocratic flow with UV detector. The mobile phase at a flow rate of 1.0 mL/min consisted of acetonitrile, methanol, and 0.01 M disodium hydrogen phosphate (pH 3.5) in the ratio of 50:35:15 v/v. Results: A linear response was observed over the concentration range 5-50 μg/mL of propranolol and the concentration range 4-32 μg/mL of valsartan. Limit of detection and limit of quantitation for propranolol were 0.27 μg/mL and 0.85 μg/mL, and for valsartan were 0.45 μg/mL and 1.39 μg/mL, respectively. The method was successfully validated in accordance to ICH guidelines acceptance criteria for linearity, accuracy, precision, specificity, robustness. Conclusion: The analysis concluded that the method was selective for simultaneous estimation of propranolol and valsartan can be potentially used for the estimation of these drugs in combined dosage form.

Transdermal potential and anti-arthritic efficacy of ursolic acid from niosomal gel systems.

The aim of the present study was to optimize niosomes by experimental design for enhanced transdermal delivery of ursolic acid for the effective treatment of arthritis. The experimental design (3 factor 3 levels, Box-Behnken design) was used to study individual and combined effects of different formulation variables. The variables cholesterol (X1), span 60 (X2) and phospholipid (X3) were taken as independent factors and their effect was observed on size (Y1) entrapment efficiency (Y2), and transflux (Y3). The formulation composition with span 60 (85mg), cholesterol (12.3mg), and phospholipid (65mg) was found to fulfil requisites of optimized ursolic acid niosome formulation (URNF). URNF had shown vesicle size of 665.45nm, entrapment efficiency of 92.74% with transflux of 17.25μg/cm(2)/h. The in vivo bioactivity showed that the prepared URNF-gel was able to provide good anti-arthritic activity due to enhanced permeation of UA through the skin and results were found to be comparable to standard gel (Omni gel). The radiographical image confirmed that, the developed URNF-gel was found to be effective to treat arthritis. Thus niosomal gel of ursolic acid would be a promising alternative to conventional therapy for safe and efficient treatment of arthritis and musculoskeletal disorders.

Enhanced transdermal delivery of luteolin via non-ionic surfactant-based vesicle: quality evaluation and anti-arthritic assessment

Abstract Luteolin (LUT) is a promising molecule with potential anti-arthritic activity. This investigation presents formulation and evaluation of niosomal transgel for enhanced transdermal delivery of LUT. Different non-ionic surfactants and vesicle compositions were employed for preparation of niosomes. The vesicle size analysis showed that all vesicles were in the range from 534.58 to 810.22 nm which favoured efficient transdermal delivery. The entrapment of LUT in vesicle was found to be higher in all surfactant. The developed formulation was proved significantly superior in terms of amount of drug permeation with an enhancement ratio of 2.66 when compared to a control formulation. The in vivo bioactivity studies revealed that the prepared niotransgel formulation of LUT was able to provide good anti-arthritic activity and the results were comparable to standard (diclofenac gel for anti-arthritic and analgesic). Finally, the results were confirmed through radiological analysis which proved that the prepared niotransgel was effectively able to treat arthritis and results were comparable with the standard formulation.

Neuroprotective study of Nigella sativa-loaded oral provesicular lipid formulation: in vitro and ex vivo study

Abstract Aim: The aim of this research was to develop proniosome (niosomes) of Nigella sativa (NS) to improve its drug release, gastrointestinal (GI) permeation and neuroprotective activity. Materials and methods: Proniosomes were prepared by thin film method using various compositions of nonionic surfactants, cholesterol, and phosphatidylcholine. The optimum influence of different formulation variables of NS such as surfactant type, phosphatidylcholine and cholesterol concentration were optimized for size and entrapment efficiency. Results and discussion: Results indicated that prepared niosome showed smaller size with high entrapment efficiency. The permeation enhancement ratio was found to be 2.16 in comparison to control with maximum flux value obtained was 7.23 µg/cm2/h for formulation NS6. The in vivo study revealed that the niosomal dispersion significantly improved neuroprotective activity in comparison to standard and control formulation. Conclusion: In conclusion, developed proniosomal formulation could be one of the promising delivery system for NS with better drug release and GI permeation profiles and improved neuroprotective activity and merits for further study.