Optimized Microemulsion Formulation Research Articles

Formulation and Characterization of Glucosamine Sulphate Potassium Chloride (GSPC) Loaded Emulgel for the Treatment of Osteoarthritis.

Osteoarthritis (OA) is becoming a major medical burden worldwide due to changing lifestyles and aging populations. Osteoarthritis is a disease characterized by a variety of anatomic and physiological changes to joints, including cartilage degradation, bone remodeling, and the formation of osteophytes. These changes cause pain, stiffness, swelling, and limitations in joint function. Glucosamine serves as a fundamental constituent for cartilage, the resilient connective tissue responsible for cushioning joints. Glucosamine Sulphate Potassium Chloride (GSPC) supplementation is widely employed to mitigate symptoms linked to osteoarthritis, a degenerative joint disorder hallmarked by cartilage degradation. Palliative care aims at minimizing pain and disability and improving function, performance, and quality of life. In this study, the emulgel formulation of GSPC was developed and checked for its potential. Currently, OA does not have a definitive treatment. Since conventional dosage forms cannot deliver the active drug content at a predefined target site in a predictable manner throughout the treatment period, a new carrier system is always required. Considering their reduced size, targeting potential, and site specificity, nanocarrier-based approaches could hold an answer to shortcomings associated with conventional routes. Thus, the objective of the current study was to formulate and characterize glucosamine sulphate potassium chloride-loaded emulgel for the treatment of osteoarthritis. Microemulsion of glucosamine sulphate potassium chloride was formulated using a spontaneous emulsification method comprising of oleic acid (oil phase), Tween 80, Tween 20 (surfactant) and PEG 400, Span 80 (co-surfactant), and distilled water (aqueous phase). The microemulsions were evaluated for surface morphology, globule size, poly-dispersibility index (PDI), zeta potential, and viscosity, and the final batch of microemulsions was selected. The optimized microemulsion contained 35% co-surfactant (propylene glycol), 20% surfactant (Tween 20), and 15% oil (oleic acid) and glucosamine sulphate potassium chloride in a dose of 60 mg, which has sufficient drug loading capacity with a droplet size of 182 nm for optimized formulation. The optimized microemulsion formulation was added to gel prepared by Carbopol 934 in a 1:1 (w/w) ratio, leading to the formulation of glucosamine sulphate potassium chloride- containing emulgel. The prepared emulgel was further evaluated for viscosity, drug content, pH, and in-vitro drug release. Emulgel formulation (F6) showed 88% drug release after 6 hours, and it followed the Higuchi model. Glucosamine Sulphate Potassium Chloride (GSPC) is used in the treatment of OA by increasing the production of proteoglycans, which can cause the cartilage to break down. Emulgel formulation (F3) showed 75.41% drug release, and formulation (F6) showed 88% drug release after 6 h. Therefore, it may be concluded that an emulgel of GSPC can be used as a controlled-release dosage form of the drug for local application in OA.

Acacetin-loaded microemulsion for transdermal delivery: preparation, optimization and evaluation

Context Acacetin is reported as a potential drug candidate for the treatment of atrial fibrillation. However, clinical applications are limited by poor water solubility, limited ethanol solubility, and extremely low oral bioavailability. Objective The present study prepared and evaluated acacetin-loaded microemulsion (ME) to achieve efficient pharmacokinetics together with no or minimal invasiveness for transdermal delivery. Materials and methods The formulation of ME was determined by the water titration method based on solubility results. The optimized formulation was achieved by the simplex lattice experiment design. The optimized ME formulations FA, FB and FC (FA with 10% and 50% DMSO as enhancers, respectively) were evaluated by ex vivo permeation with Franz diffusion cell and excised mice skin. In vivo pharmacokinetic studies were also performed at 8 mg/kg in rats within 6 h by transdermal administration. Results The optimal ME (FA) was comprised of 12.2% caprylic acid decanoate monoditriglyceride (MCF-NF), 39.8% Smix (RH40: Trans = 2:1 w/w) and 48% water, respectively. Acacetin-loaded FA with particle size 36.0 ± 3.6 nm and drug solubility 803.7 ± 32.1 mg/g was prepared. FB had significantly higher cumulative amounts and higher AUC0-∞ (196.6 ± 11.0 min × μg/mL, p < 0.05) than that FA alone (121.4 ± 33.1 min × μg/mL). Discussion and conclusions The formulation of ME combined with the penetration enhancer can effectively improve the solubility and percutaneous absorption efficiency of acacetin, providing a new option for the non-invasive delivery of acacetin.

Topical Delivery of Diacetyl Boldine in a Microemulsion Formulation for Chemoprotection against Melanoma.

This study aimed to develop a microemulsion formulation for topical delivery of Diacetyl Boldine (DAB) and to evaluate its cytotoxicity against melanoma cell line (B16BL6) in vitro. Using a pseudo-ternary phase diagram, the optimal microemulsion formulation region was identified, and its particle size, viscosity, pH, and in vitro release characteristics were determined. Permeation studies were performed on excised human skin using Franz diffusion cell assembly. The cytotoxicity of the formulations on B16BL6 melanoma cell lines was evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay. Two formulation compositions were selected based on the higher microemulsion area of the pseudo-ternary phase diagrams. The formulations showed a mean globule size of around 50 nm and a polydispersity index of <0.2. The ex vivo skin permeation study demonstrated that the microemulsion formulation exhibited significantly higher skin retention levels than the DAB solution in MCT oil (Control, DAB-MCT). Furthermore, the formulations showed substantially higher cytotoxicity toward B16BL6 cell lines than the control formulation (p < 0.001). The half-maximal inhibitory concentrations (IC50) of F1, F2, and DAB-MCT formulations against B16BL6 cells were calculated to be 1 µg/mL, 10 µg/mL, and 50 µg/mL, respectively. By comparison, the IC50 of F1 was 50-fold lower than that of the DAB-MCT formulation. The results of the present study suggest that microemulsion could be a promising formulation for the topical administration of DAB.

FORMULATION OF NANOSTRUCTURED LIPID CARRIERS OF HALOPERIDOL PREPARED BY USING CLARIFIED BUTTER

Objective: To develop the nanostructured lipid carriers (NLC’s) using clarified butter. Methods: Haloperidol-loaded microemulsion templates were prepared by using Smix of Tween 80 and propylene glycol in the ratio 1:2. The selection of the mixture of surfactant and co-surfactant (Smix) and their appropriate proportion were decided by the traditional way of construction of pseudo ternary phase diagrams. 22 factorial design was used to check the amenability of the formulation for its successful scale-up. Sonication time and the amount of Smix were selected as independent variables and their influence on the globular size (Y1) of the microemulsions formed was evaluated by using statistical models. Composition of the optimized microemulsion template was further used to prepare haloperidol-loaded NLC’s by ‘microemulsion quenching method’. Results: The microemulsion formulations containing Tween 80 as a surfactant and propylene glycol as a co-surfactant exhibited the smallest globular size and hence this composition was used further to implement factorial design as design of experiments. The statistical analysis of the data suggested that the microemulsion formulation can be scaled up successfully. NLC’s were prepared from the optimized microemulsion formulation as template. The globular size of NLC’s was confirmed by Transmission Electron Microscopy and was observed to be in the range of 300 to 600 nm. Conclusion: The present work suggested that the latency of the clarified butter as a natural blend of solid lipid and liquid lipids can be successfully explored to prepare nanostructured lipid carriers.

DEVELOPMENT AND CHARACTERIZATION OF PLANT OIL-BASED POTENT ANTICHOLINESTERASE MICROEMULSION CONTAINING WITHANIA SOMNIFERA EXTRACT WITH ENHANCED TRANSDERMAL DELIVERY OF PHYTOCONSTITUENTS FOR THE TREATMENT OF COGNITIVE DISORDERS

Objective: This work was carried out to develop Cymbopogan Citratus (lemon grass)oil based microemulsion formulation loaded with the extract of Withania somnifera which possess enhanced transdermal delivery of phytoconstituents with anticholinesterase activity useful in treating Alzheimer’s disease. Methods: Methanolic extract of Withania somnifera roots were prepared and it was investigated for the inhibition of acetylcholinesterase (AChE) activity by Ellman’s assay. Based on the acetylcholinesterase activity, the specific amount of extract was loaded on to the microemulsion formulation. The Cymbopogan Citratus oil, tween 20, ethanol was used as oil phase, surfactant, and cosurfactant, respectively, for the preparation of microemulsion. Pseudo ternary phase diagram was constructed using a water titration method. The microemulsion formulations were characterized for droplet size, PDI, zeta potential and drug content. The optimized formulation was subjected to in vitro drug release and permeation studies and compared with the extract. Results: IC50 value of ashwagandha extract for anticholinesterase activity was found to be 68.73 µg/ml. The optimized microemulsion formulation had droplet size of 199.9±0.3 nm with PDI 0.029±0.2, zeta potential of-19.49±0.7mv and drug content was found to be 97.5±1.3%. The optimized microemulsion formulation showed 85±1.02% release of withaferin A after 24 h of in vitro drug release study. The prepared microemulsion loaded with ashwagandha extract showed excellent permeation of withaferin A(1.4µg/cm2/min) than the flux obtained from extract solution (0.7µg/cm2/min). Conclusion: Optimised microemulsion formulation is suitable for transdermal delivery of anticholinesterase phytoconstituents from ashwagandha extract hence useful in the treatment of Alzheimer’s disease

Design, Development and in vitro Assessment of Flurbiprofen Microemulsion Gel for Transdermal Drug Delivery

The aim of current research is to develop flurbiprofen microemulsion gel for transdermal delivery. To prepare a microemulsion oil, surfactant and co-surfactant selection is one of the important criteria. Selected to prepare different ratios of oil and surfactant mixture using ternary phase diagram. Based on results of physicochemical properties, we have optimized one formulation. The optimized microemulsion formulation incorporated into carbopol P 934 gel base. The In vitro diffusion of drug release shown maximum (98.6% in 12hrs) for prepared microemulsion gel than marketed gel (60.5% in 16 hrs).

Comparison of Microemulsion and Solvent Evaporation Technique for Solubility Enhancement of Amlodipine Besylate

Introduction: Amlodipine besylate is a calcium channel blocker indicated for hypertension and angina. It is described as slightly soluble in water and due to its limited solubility, it may result in poor bioavailability. The aim of this study is to enhance the solubility of amlodipine besylate using solvent evaporation method and microemulsion technique and to compare the two methods. Method: Solid dispersions (SD) of amlodipine besylate were developed by employing solvent evaporation method. PEG6000 was the polymer of choice and different drug:polymer ratios were used. Evaluation of the prepared SDs include solubility studies, dissolution studies and scanning electron microscopy (SEM). As for the microemulsion technique, microemulsions were prepared by phase titration method and the optimized microemulsion formulation was then characterized for solubility studies and dissolution studies. Results: SD3 with drug:polymer ratio of 1:4 achieved the highest solubility which was 96.97 mg/ml ± 0.92 whereas the solubility of the optimized microemulsion was found to be 112.54 mg/ml ± 0.92. In solvent evaporation method, as the drug:polymer ratio increases, the solubility and dissolution rate of SDs increases. Conclusion: The two methods had significantly enhance the solubility of amlodipine besylate however the microemulsion technique showed better solubility profile.

Tavaborole microemulsion: New strategy for the targeted treatment of onychomycosis

The targeted treatment of onychomycosis becomes a major concern nowadays for onychologist considering the limited permeability of the drug formulation at the nail site due to the number of factors such as complex barrier of keratin structure inside the nail layer, drug-keratin binding properties, as well as lack of availability of promising drug delivery system. In the present study, tavaborole-loaded novel microemulsion and its gel formulation was developed, optimized, and evaluated for the targeted treatment of onychomycosis. The microemulsion formulation was designed and developed using a 32 factorial experimental design approach. The optimized microemulsion formulation consisting of tavaborole (2.5%w/w), glyceryl caprylate/caprate (7.8%w/w), polyethylene glycol-8 caprylate/capric glycerides (21.45%w/w), diethylene glycol monoethyl ether (21.45%w/w) and demineralized water (46.80%w/w) was converted to gel using carbopol® 934P (0.5%w/w). In the ex-vivo bovine hoof membrane model permeation study, the optimized microemulsion formulation exhibited higher drug permeation (116.21 ± 9.75 μg/cm2) and followed the first-order release kinetics mechanism. The in-vitro nail clipping study demonstrated enhanced penetration of tavaborole (0.872 ± 0.019 μg/mg) from optimized microemulsion formulation. It also exhibited improved antifungal activity against dermatophytes species such as Trichophyton rubrum (2.56 ± 0.086 cm), Trichophyton mentagrophytes (3.13 ± 0.097 cm), and Candida albicans (3.63 ± 0.103 cm). The microemulsion formulation did not reveal any toxic and detrimental effects of excipients on nail cells in VERO cell lines cytotoxicity study. Thus, tavaborole loaded microemulsion can be considered as a potential formulation for topical onychomycosis therapy.

Formulation and stability of silkworm pupae oil microemulsion

Because of the instability, perishable odor and peculiar smell, a microemulsion system was designed to safely and effectively supply α-linolenic acid from silkworm pupae oil. Microemulsion-loaded silkworm pupae oil was prepared from isoamyl acetate, castor oil polyoxyethylene ether 35 (EL-35), ethanol and water. The optimal microemulsion formulation was a 4% composite oil phase (silkworm pupae oil: isoamyl acetate, 1:2), 16% composite surfactant (EL-35: ethanol, 2:1) and 80% water, with uniformly dispersed spherical particles with diameters of 16.25 nm. The color of the microemulsion was transparent and had no peculiar smell. The investigation results of environmental stress show that the transmittance is 86%–99%, and there is no significant difference from the control group (p > 0.05). Compared with silkworm pupae oil, the total antioxidant capacity of the microemulsion was increased by 7.70 times. Microemulsion-loaded silkworm pupae oil exhibited good physical and antioxidation stability. This work provides a feasible new scheme for ensuring the nutritional and health functions of silkworm pupae oil and supplying α-linolenic acid safely and effectively.

Brain-Targeted Intranasal Delivery of Zotepine Microemulsion: Pharmacokinetics and Pharmacodynamics.

The purpose of our study was to improve the solubility, bioavailability, and efficacy of zotepine (ZTP) by brain-targeted intranasal delivery of microemulsion (ME) and its physicochemical properties, the pharmacokinetic and pharmacodynamic parameters were evaluated. The optimized ME formulations contain 10% w/w of oil (Capmul MCM C8, monoglycerides, and diglycerides of caprylic acid), 50% w/w of Smix (Labrasol and Transcutol HP, and 40% w/w of water resulting in a globule size of 124.6 ± 3.52 nm with low polydispersity index (PDI) (0.212 ± 0.013) and 2.8-fold higher permeation coefficient through porcine nasal mucosa compared to pure drug). In vitro cell line studies on RPMI 2650, Beas-2B, and Neuro-2A revealed ZTP-ME as safe. ZTP-ME administered intranasally showed higher AUC0–t24 (18.63 ± 1.33 h × µg/g) in the brain by approximately 4.3-fold than oral ME (4.30 ± 0.92 h × µg/g) and 7.7-fold than intravenous drug solutions (2.40 ± 0.36 h × µg/g). In vivo anti-schizophrenic activity was conducted using catalepsy test scores, the formulation showed better efficacy via the intranasal route; furthermore, there was no inflammation or hemorrhage in the nasal cavity. The results concluded that the ZTP microemulsion as a safe and effective strategy could greatly enhance brain distribution by intranasal administration.

Formulation and evaluation of a α-linolenic acid and vitamin E succinate microemulsion with low surfactant content and free of co-surfactant for use as a nutritional supplement

Herein, we have designed an alcohol-free and low-surfactant microemulsion to safely and effectively supply α-linolenic acid (ALA) and vitamin E (VE). Ternary phase diagrams show that the use of medium- or short-chain alcohols as the co-surfactant (CoS) was unfavorable for the formation of the ALA microemulsion due to the competitive hydrogen bonding effect and vitamin E succinate (VES) significantly increased the ALA microemulsion region by improving the hydrophilicity of the oil phase. The optimal microemulsion formulation (Mav) was 6.86% ALA, 1.14% VES, 12% surfactant and 80% water, with uniformly dispersed spherical particles with diameters of ~ 25.41 nm and viscosity of 35.17 mPa·s. The Mav was stable to high temperature, ionic strength and pH, and exhibited good physical and anti-oxidation stability. The Mav facilitated the release and hydrolysis of VES, indicating that the CoS-free microemulsion with low surfactant content is promising for the safe and effective supply of ALA and VE.

Development and in vitro Characterization of Intranasal Microemulsions of Sumatriptan Succinate for brain Targeting

Microemulsions, by virtue of their lipophilic nature and low globule size, are widely explored as a delivery system to enhance uptake across mucosa. The main aim of the present investigation is to develop and in vitro characterization of intra nasal microemulsion of sumatriptan succinate for brain targeting for treating acute attack of migraine. The liquid microemulsion was prepared by dissolving drug (sumatriptan succinate) and mucoadhesive polymer sodium alginate in double distilled water. The prepared microemulsion was evaluated for particle size measurement, zeta potential measurement, viscosity measurement, centrifugation, drug content, optical clarity and in vitro drug release studies. The prepared formulations were showed particle size in the range of 106.2±2.03 to 282.8±2.51. The zeta potential value of the formulation ME2 showed −32.0mv indicating negative surface charge. The drug content showed in the range of 89.3±0.242 to 94.3±0.128. the optimized formulation showed in vitro drug release 74.2±0.95% at 12 h. and 86.23±0.41% at 24 hrs. From the results it was concluded that the prepared optimized microemulsion formulation as drug delivery system to improve bioavailability of the drugs like sumatriptan succinate.

Design and evaluation of microemulsion-based efinaconazole formulations for targeted treatment of onychomycosis through transungual route: Ex vivo and nail clipping studies

The onychomycosis treatment remains a big challenge for onychologist due to the shorter nail residence time of topical formulations and the lack of availability of novel formulations in markets for new generation antifungal drugs. The objective of this work was to design, develop, optimize, and evaluate microemulsion formulations for effective delivery of efinaconazole through transungual route in onychomycosis treatment. Capmul® MCM (Glyceryl Caprylate/Caprate) as oil, Labrasol® (caprylocaproyl polyoxyl-8 glycerides) as a surfactant, and Transcutol® P (diethylene glycol monoethyl ether) as co-surfactant exhibited higher solubility of efinaconazole and surfactant-cosurfactant mixture (Smix) in a ratio of 1:1 rendered higher microemulsion region in the pseudo-ternary phase diagram. The optimized microemulsion formulation containing 6%w/w oil phase, 22.5%w/w surfactant, 22.5%w/w co-surfactant, and 49%w/w demineralized water was converted into gel formulation using 1.0%w/w Carbopol® 934 P gelling agent and evaluated for stability of 6 months. The optimized microemulsion formulation globule size was less than 100 nm. The ex vivo permeation confirmed improved permeation of efinaconazole from microemulsion formulations (346.36±12.90μgcm−2) in comparison to reference formulation without observing any lag in drug permeation through the nail plate. The in vitro antifungal study data indicated increased antifungal efficacy relative to efinaconazole topical solution against Trichophyton rubrum, Trichophyton mentagrophytes, and Candida albicans species. Further, an in vitro cell cytotoxicity study exhibited no toxic effect for any excipients used in the formulation while applied on nail cells. Hence, the efinaconazole loaded microemulsion formulations could be considered as an effective therapy in the treatment of onychomycosis.

Microemulsion and microemulsion gel formulation for transdermal delivery of rutin: Optimization, in-vitro/ex-vivo evaluation and SPF determination

In this research work, the designation of a new microemulsion formulation for the transdermal application of rutin was investigated. After the construction of pseudo-ternary phase diagrams containing tween 80 as a surfactant, ethylene glycol as co-surfactant and IPM (Isopropyl myristate) as the oil phase, the D-optimal mixture experimental design was used for the optimization process. The independent variables were oil, surfactant/co-surfactant and water weight concentrations and the two response variables were rutin solubility in microemulsions and drug release from microemulsions. After that, physicochemical characterization and stability studies were performed. In the other part the rutin, as an active pharmaceutics agent was loaded in the optimized microemulsion formulation to study kinetic of its release and sun protection factor. To investigate the ex-vivo skin permeation and retention of the drug from the carriers, the optimized formulation and its gel form, were examined on rat skin at similar conditions. The proposed formulation showed different release rate, skin permeation, sun protection factor and particle size, compared to recent works. Obtained results indicated that the microemulsion formulation can be used, especially in gel form, as an effective vehicle for prolong transdermal delivery of rutin desirably in sunscreen formulations.

Antioxidant in cosmeceutical products containing Calophyllum inophyllum oil

Every part of Calophyllum inophyllum L. has been used in various traditional remedies, especially the oil from its nut was mostly used to treat skin diseases. This study aimed to investigate the composition and antioxidant activity of C. inophyllum nut oil and formulate the oil as a cosmeceutical product. The chemical composition and the amount of total phenolic compounds (TPC) were demonstrated by Gas Chromatograph-Mass Spectrometer (GC-MS) and Folin–Ciocalteu method, respectively. Additionally, the antioxidant activity was tested using the DPPH method. Calophyllolide (4.35%) was a major component. Additional components were calanolide A, inophyllum D, and inophyllum B. We found that the TPC contained 25.9 ± 1.2 mg GE/g oil and a free radical scavenging activity approximate to that of the synthetic Trolox. Emulgel formulation consisted of tween 80, span 80, and isopropyl alcohol as a surfactant, and carbopol 940 as a gelling agent. The microemulsion was formulated using distilled water, oil, tween 80 with span 80, as a surfactant, and isopropyl alcohol as a cosurfactant. The mean droplet size for optimized microemulsion formulations was 34.37 ± 1.06 nm. Furthermore, the results of thermodynamic stability tests (freeze-thaw cycle) and long-term stability tests indicated that emulsions and microemulsions remained stable. In conclusion, this nut oil could potentially be used as a cosmeceutical product, and the obtained emulgels and microemulsions exhibited good characteristics in terms of being a potential agent for skin antioxidant.

DEVELOPMENT OF MICROEMULSION FORMULATION FOR ORAL DELIVERY OF ROSUVASTATIN CALCIUM

The purpose of conducting this study was to prepare an oral microemulsion formulation of Rosuvastatin calcium (RC) to improve its water solubility. Oil in water microemulsion was formulated using Oleic acid, Tween 80 and Polyethylene Glycol-400(PEG-400) as oil, surfactant and co-surfactant, respectively. The ideal proportion of surfactant: co-surfactant (Smix) was chosen by constructing pseudoternary diagrams. The microemulsion formulations which proved to be stable after thermodynamic stability testing were further evaluated for physical characteristics. Selected formulations were evaluated for droplet size, zeta potential, polydispersity index, viscosity and % drug content. The results were suggestive that optimized microemulsion formulation (F2) was thermodynamically stable and clear having a droplet size of 74.29 nm and zeta potential of -18.44. In vitro dissolution study for optimized microemulsion was performed using a dialysis bag method and cumulative % drug release was determined. The result from the release study was indicative of improved solubility of Rosuvastatin calcium which may serve to boost up the oral bioavailability of drug.

Development of Intranasal Mucoadhesive Microemulsions of Levodopa for the Treatment of Parkinson’s Disease: Pharmacokinetics and Pharmacodynamic Evaluation in Rat Model

Levodopa (L-DOPA) is a first line drug for treating Parkinson’s disease and prescribed in combination with carbidopa orally and is associated with nausea and poor bioavailability. In the present work levodopa microemulsions were developed, administered intra nasally and pharmacokinetics Plasma, brain, pharmacodynamics were evaluated in comparison to oral route in rat model. Levodopa microemulsions (ME) were prepared by water titration method. Optimized formulation (ME16) was composed of oil (Oleic acid), Smix (Tween 80: PEG400: Ethanol; 1:1:0.25) water and drug in the ratio 5:60:35:2.5. The globule size, zeta potential and steady state flux of the optimized formulation were 96 nm, -33.6 mV and 57.53μg/cm2/h respectively. Chitosan was added at 0.5% concentration to optimized microemulsion formulation as permeation enhancer. The flux of the MME was significantly higher (70.29μg/cm2/h) than microemulsion. The zeta potential of MME was 13.2 mV which is due to presence of cationic polymer. The formulations ME16 and MME showed significantly higher flux which is 3.09 and 3.78 times higher than drug solution. The pharmacokinetics plasma, brain and pharmacodynamic studies were carried out on male wister rats. Bioavailability of ME brain was 1.6 times and MME brain was 3.06 folds to oral drug solution The drug targeting efficiency (DTE) and direct nose to brain transport (DTP%) were 2.77 and 66.7% for MME and 1.72 ,45.57% for ME which were significantly high compared to oral drug solution (0.9). Antiparkinson’s activity of optimized formulation, drug solution via nasal route in comparison to oral solution was studied in rotenone induced male wistar rats. Optimized ME16 and MME formulation treated group showed significant increase (P<0.001) in rat weight, locomotor activity by photoactometer and grip strength on rotarod. Biochemical parameters of brain homogenates of ME and MME treated groups showed significant reduction in levels of lipid peroxides, nitric oxide and total protein and significant increase in reduced Glutathione (P<0.0001) compared to drug solution treated by both oral and nasal route. Therefore, Intranasal route could be better alternative to improve brain targeting efficiency and reduce adverse effects of levodopa especially when administered as microemulsion.

Development and Ex vivo evaluation of Rasagiline Mesylate mucoadhesive microemulsion for intranasal delivery using Box-Behnken design

Rasagiline mesylate (RM), an irreversible, selective inhibitor of MAO-B enzyme, is used in the treatment of Parkinson’s disease as oral tablets. It has low oral bioavailability (36%) due to hepatic first pass metabolism. Oral route of administration is associated with nausea and vomiting. Hence present research work was aimed to develop intranasal RM- loaded mucoadhesive microemulsions for brain targeting via olfactory pathway. The microemulsions were developed using Box Behnken design and evaluated for globule size, PDI, Zeta potential, pH, viscosity and ex vivo permeation on excised porcine nasal mucosa. Based on drug solubility, Capmul MCM, Tween 20 and Transcutol P were selected as oil, surfactant and cosurfactant respectively. Microemulsions were prepared by water titration method. Pseudoternary phase diagrams were constructed and the levels of surfactants, oil were selected. The influence of independent variables such as oil, Smix and water on responses size, zeta potential and flux were studied with the help of polynomial equations, contour plots and 3D response surface plots generated by design expert software. Optimized microemulsion formulation (ME18) was composed of oil (Capmul MCM), Smix (Tween 20: Transcutol P; 1:1), water and drug in the ratio 5:42:65:5.The globule size, zeta potential and flux of the optimized microemulsion was 150 nm, -29.6 mV and 291.7 μg/cm2/h respectively. Mucoadhesive agent (Chitosan) was added at 0.5% concentration to optimized microemulsion formulation (MME18). The size, zeta potential and flux of the MME18 was 176.4 nm, 12.1 mV and 323.1 μg/cm2/h respectively. The flux of ME18 and MME 18 was significantly higher than drug solution. The enhancement ratio of MME 18 was 4.2 times to that of drug solution, indicating potential advantage of microemulsion formulation.

PREPARATION AND EVALUATION OF MICROEMULSION CONTAINING ANTIHYPERTENSIVE DRUG

Objective: The aim of the present study was to design novel drug delivery system containing ramipril microemulsion. Ramipril is an antihypertensive drug having very low aqueous solubility and bioavailability. Ramipril microemulsion could be used as a possible alternative to the traditional oral formulation to improve dissolution rate and hence its bioavailability with avoidance of the first-pass metabolism.Methods: The microemulsion existence region was determined by constructing pseudoternary phase diagram and prepared by using four components orange oil, tween 80 as a surfactant, propylene glycol as co-surfactant and distilled water as the aqueous phase. The water titration method was employed for its determination. All formulated microemulsion were subjected for visual inspection, centrifugation and stability test. The all stable formulations were selected for further study.The optimized microemulsion formulation B-9 was subjected for various evaluation parameters such as, visual inspection, stability studies, pH, viscosity measurements, electrical conductivity, content uniformity and dye solubility test.Results: Results revealed that construction of phase diagram and use of phase titration method was a suitable technique for the preparation of microemulsion as most of the formulations were transparent. It was found that the best microemulsion result was found for ratio 2:1. The results of stress tests conclude that the optimized formulation was both physically and chemically stable for 8 mo. Also, The Fourier transform infrared (FTIR) radiation measurement and Differential scanning calorimetry (DSC) of optimized formulation indicate the compatibility of ramipril with orange oil, surfactant-tween 80 and cosurfactant-propylene glycol. From electrical conductivity 0.283 σ and staining test the prepared optimized formulation B-9 was found to be o/w type of microemulsion. The optimized B-9 formulation showed good viscosity 13.52±0.01cps and pH 3.21±0.02 with highest drug content uniformity was found to be 84.98±0.02 %.Conclusion: In the present study a satisfactory attempt was made to formulate a novel o/w microemulsion of ramipril which improves the gastrointestinal absorption by raising its water solubility and hence oral bioavailability is also enhanced.

A novel approach to Lithol red nanopigment by water in oil microemulsion method

Lithol Red is one of the commonest 20th century red synthetic organic pigments. It is used in various printing industry for its brightness and bleed-resistance. Performance of pigments depends on their size completely. In the current research, microemulsion as simple and novel method has been applied for the preparation of Lithol red nanopigment. The optimized microemulsion formulation contains water 15%, n-butyl acetate 55%, cethyl trimetyl ammonium bromide (CTAB, as cationic surfactant) 15% and 2-propanol (as co-surfactant) 15%. Lithol red nanopigments are characterized by SEM and TEM. Prepared Lithol red nanopigments were spherical with the average diameter of 60 nm and low size distribution.