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A widespread of superficial fungal infections deals with concerns related to current therapeutic regimen such as drug resistance and adverse events associated with the same which leads exploration of natural oils as an antifungal agent. The aim of present work is to the development of clove oil loaded microemulsion based gel for treatment of superficial fungal infections. The microemulsion based gel was prepared by phase titration method and optimized using D-optimal design considering globule size, drug permeation and drug retention on skin as critical quality attributes. The MIC and zone of inhibition of clove oil was found to be 2.2 mg/ml and 38 mm respectively. A pale to yellowish transparent microemulsion had a globule size, zeta-potential and PDI of 14.41 nm, 0.73 and 0.0113 respectively indicating a stable microemulsion. A clove oil loaded microemulsion based gel (CLMBG) with a pH of 6.27 and viscosity of 12.87 m.pas/sec exhibited a comparable texture profile to marketed preparation. The drug release of the CLMBG with a drug content of 102.6 ± 4% in acetate buffer pH 5.5 was 98.5 ± 0.35% ensuring complete drug release from the formulation. Ex-vivo drug permeation study and skin irritation study dictated the retention of drug at site of action and the formulation to be non-irritant. The antifungal study proved the formulation to have similar efficacy as the marketed product (clobet gel). The stability study indicated the product to be safe, efficacious and stable formulation. From the above results, it can be derived that clove oil loaded microemulsion based gel can be a promising alternative to current antifungal regimens.

The present study was investigated to design and characterize Domperidone (DM) loaded mucoadhesive microemulsion for enhanced systemic absorption through nasal delivery. Domperidone is a dopamine antagonist non-CNS drug, possessing high log P and extensive hepatic metabolism. The different microemulsion compositions were prepared by water titration method and optimized by D-Optimal mixture design. The screening criteria for optimization of formulation were drug loading, globule size, spray angle, spray pattern, mucoadhesion time, in-vitropermeation and in-vivopharmacokinetic profile. A microemulsion formulation comprising of oleic acid (8%), labrasol (32.5%), propylene glycol (32.5%) and water (27%) was found optimum. The spray droplets were rendered mucoadhesive by optimum quantity of PEO P7 (0.5% w/w). The globule size, mucoadhesion time and cumulative amount of drug permeated (after 240 min) of optimized formulation were 25 nm, 17 ± 2.0 min, and 80.14 ± 13.47 μg cm−2, respectively. Pharmacokinetic study of developed formulation revealed significant difference (p < 0.05) in Cmax(48.34 ng/mL) and AUC0→∞(6204 ng*h*mL−1) compared to DM solution and Domstal®, indicating enhanced bioavailability through nasal route. Safe and non-irritant nature of the formulation was proven by no severe histological changes reported in nasal irritation study. Biodistribution study exhibited least amount (2.12 ± 0.4%) of brain uptake confirming systemic absorption of drug.

Objective: The purpose of the study was to formulate and evaluate thiolated chitosan based nanoparticulate mucoadhesive ophthalmic in situ gelling system of prulifloxacin for bacterial keratoconjunctivitis. Method: Low molecular weight chitosan was modified to thiolated chitosan in the laboratory and confirmed with FTIR and DSC studies. Thiolated chitosan nanoparticles were prepared and incorporated in a polymeric sol-gel system containing prulifloxacin for the ophthalmic drug delivery. The prepared formulation was characterized for the various physicochemical properties i.e., particle size, zeta potential, gelation time, mucoadhesion strength study and the optimized formulation was characterized for in vitro drug release study, ocular irritation study, antimicrobial efficacy study and stability study etc. Results: Gelation pH was found to be 7.2±0.2. The acquired SEM images of the optimized NPs showed good mean particle size below 16 nm. Drug entrapment efficiency was found to be more than 80%. PFL-TCS loaded NPs sol-gel system showed sustain release for a period of 12 hours. It was also confirmed that the formulation was non-irritant to the eye. Conclusion: The developed formulation was found to be a better alternative to the conventional ophthalmic formulations.

Present study attempts to overcome pH-dependent solubility, a limitation for oral delivery of poorly soluble BCS class-II drugs. A pH independent, patient compliant, dual working gastroretentive drug delivery system of model drug quetiapine fumarate (QF) was fabricated by unique combination approach of mucoadhesion and floating. Bilayer tablets comprising floating adhesive layer (FL) and matrix layer (ML) was systematically optimized by applying 32full factorial experimental designs. Selected variables for FL: Polyox®303WSR (X1FL) and alginate beads (X2FL), and for ML: HPMC K100M (X1ML) and fumaric acid (X2ML) were studied against responses for FL: floating lag time (R1FL), total floating time (R2FL) and adhesion force (R3FL) and for ML: percentage drug released at 2 h—Q2h(R1ML), 8 h—Q8h(R2ML), and 18 h—Q18h(R3ML), respectively. Optimized batch (OP) showed floating lag time (6.5 h), total floating time (14 h), adhesion force (0.82 N) and Q18h(>90 %). Pharmacokinetic study of OP and immediate release market product demonstrated improved bioavailability (~12 % higher AUC0–∞) of OP. In a nutshell, developed drug delivery system can be fabricated as a platform for QF and similar BCS class-II drugs with pH dependent solubility.

The objective of the present investigation was to prepare phenytoin microemulsion for intranasal administration by application of experimental design. Phenytoin microemulsion was prepared by water titration method. The concentration of oil (X1), surfactant (X2) and cosurfactant (X3) were selected as independent variables, in a simplex centroid design, from microemulsion region obtained from pseuodoternary phase diagram while the globule size (Y1) and cumulative phenytoin diffused at 60 min (Y2) through sheep nasal mucosa were taken as dependent variables. Mathematical models were generated for the response variables. The validity of the generated equations was established using check point batches. Microemulsion that had a smaller globule size of dispersed phase and high level of % drug diffusion was desirable. The generated mathematical equations were used to identify the desirable zone where all the criteria for the responses were satisfied and an optimum batch was recognized. Ex-vivo study of optimum microemulsion on sheep nasal mucosa shows absence of nasal toxicity. It was found that faster recovery from seizures was obtained in rats treated with intra nasal phenytoin microemulsion in comparison to the rats treated with oral microemulsion and nasal solution. Higher concentration of phenytoin was found in rats treated with intranasal microemulsion in comparison to the rats treated with phenytoin solution administered intraperitoneally. Gamma scintigraphy results also suggested faster availability of drug into brain when microemulsion was administered intranasally.

Intravenous iron formulations comprising of iron/iron–oxyhydroxide–carbohydrate complex are an established therapy for the treatment of iron deficiency anemia. These preparations should be subjected to exhaustive physicochemical and toxicological studies in order to establish their safety and efficacy. Following Venofer®(innovator iron–sucrose formulation), various iron sucrose similar have entered into the market with equivalent physicochemical and toxicological profile. This report describes the physicochemical and toxicological studies of a novel iron sucrose injection (IS-Claris). IS-Claris and Venofer®were subjected to various physicochemical studies such as elemental and chemical analysis; X-ray diffraction; particle size and distribution; labile iron detection, Mössbauer and Raman spectroscopy. The presence of iron oxides in IS-Claris and Venofer®could be confirmed by the major peaks at 24.65° (2θ) and 38.2° (2θ). The iron sucrose samples demonstrated similar reduction peaks of Fe(III) to Fe in their respective polarograms. The average diameter of the core of IS-Claris and Venofer®was estimated to be 2.92 ± 0.01 and 2.77 ± 0.63 nm, respectively. The Mössbauer spectra of IS-Claris and Venofer®showed a doublet with an isomer shift δ = 0.43 ± 0.01 mm/s. Moreover, the other physicochemical specifications of IS-Claris were comparable to Venofer®. The toxicological studies demonstrated that IS-Claris safety profile is equivalent to Venofer®. It could be concluded that IS-Claris could be used as a potential alternative to Venofer®with similar clinical implications.

In present day, availability of various carriers, innovative techniques of production and plenty of solvents support the growth of solid dispersion (SD) technology in pharmaceutical industries to overcome many issues. The present study was aimed to develop SD based sustained release system of Milnacipran HCl (MH). The SD containing ethyl cellulose, Eudragit RLPO and Eudragit RSPO at drug–polymer ratios of 1:1, 1:2, and 1:3 were developed using solvent evaporation technique and different waxes at ratio of 1:1, 1:1.25, 1:1.5 and 1:1.75 with drug were developed by melting method. The physicochemical properties of SD were evaluated using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The desired SD batch was further compressed into tablet unit to achieve predetermined once a day drug release. Tablets prepared were evaluated for physicochemical parameters, in vitro drug release, drug release kinetics and scanning electron microscopy. Out of selected carriers, bees wax had shown maximum release retardation. The results of FTIR, DSC and XRD studies exhibited poor interaction amongst MH–bees wax and retention of crystalline state of MH in SD system. The presence of Benecel®(HPMC K 200 M; 75 mg) in tablets comprising SD (1:1.25, MH:bees wax) revealed remarkable drug release extension and it was considered an optimal. The later was submitted to short term stability study and its results indicated the stable characteristic of system. Drug release from optimized formulation fitted well into Higuchi model with anomalous diffusion. The compressed unit of SD system of highly water soluble drug can be successful single day regimen.

The present research was aimed at development and evaluation of self-nanoemulsifying drug delivery system (SNEDDS) for improving bioavailability of nelfinavir mesylate (NFV), a protease inhibitor exhibiting pH dependent solubility and variable oral bioavailability. Maisine 35-1, Cremophor RH-40, and Labrasol were identified as oil, surfactant, and co-surfactant that had best solubility for NFV. Scheffe’s mixture design was used to optimize the amount of components in liquid self-nanoemulsifying drug delivery system (L-SNEDDS) by taking their amounts as independent variable, whereas globule size, drug loading, and percent transmittance were taken as dependent variable. Optimized NFV-L-SNEDDS was then adsorbed on Neusilin US2 to form solid self-nanoemulsifying drug delivery system (S-SNEDDS). NFV loaded L-SNEDDS and S-SNEDDS were characterized for various physicochemical properties, and solid-state properties were determined through differential scanning calorimetry, X-ray diffraction, and scanning electron microscopy studies. In vitro dissolution using simulated gastric fluid and simulated intestinal fluid, ex vivo drug release study, and in vivo study were performed for pure NFV and NFV-S-SNEDDS. NFV-S-SNEDDS showed more than 90 % drug release in 20 min during drug release studies irrespective of pH of the dissolution medium. In vivo study revealed significant difference between release of NFV from suspension and NFV-L-SNEDDS and NFV-S-SNEDDS when given to rabbits (p< 0.001). NFV-L-SNEDDS and NFV-S-SNEDDS were subjected to stability study as per ICH guidelines, and NFV-S-SNEDDS was found to be stable during the period of study. S-SNEDDS could serve as a potential drug delivery system for NFV.

Present study aims at formulation and development of quick dissolving film of nebivolol hydrochloride applying simple lattice experimental design using three hetero polymers hydroxypropyl methylcellulose, pullulan and polyvinyl pyrrolidone. Films were prepared using solvent casting technique and optimized formulation was derived by desirability function. Regression equations and contour plots were executed to narrate dependent variables, i.e. percentage drug release in 30 s (Y30), tensile strength, elastic modulus, percentage elongation and load at yield, to independent variables. Results of the experimental design revealed that the independent factors hydroxypropyl methylcellulose and pullulan significantly influenced the mechanical properties and percentage drug release from the film which was ultimately reflect in the formulation of optimized batch. The high % drug release of the film in simulated saliva and simulated gastric fluid indicated that it can be successfully used in drug delivery systems for drugs with high first-pass metabolism.

The objective here was to develop gastroretentive tablets of clarithromycin to provide increased residence timein stomach for delivery of antibiotic to treat H. pylori induced gastric ulcers. Hydroxypropylmethylcellulose K4M(HPMC) was used as a mucoadhesive polymer and Avicel PH101 was used as the release modifier. Tablets containingdrug, HPMC and Avicel PH101 were prepared using wet granulation technique. The tablets were evaluated for in vitrodrug release profile and ex vivo bioadhesion property. A 3^2 factorial design was employed to study the influence ofamount of HPMC (X1) and amount of Avicel PH101 (X2) on drug release at the end of 2nd hour (Y1), 6th hour (Y2) and10th hour (Y3) from the mucoadhesive tablets. Target release profile was generated for a 12 hour dosage regimen and dissolutionprofile of the best batch was compared using similarity factor f2. Results of multiple regression analysis indicatedthat HPMC reduced the drug release at all time points while! Avicel PH101 increased the amount of drug release. The dissolutionprofile of the optimum batch had the similarity factor value of 61 indicating that the release profile was similar tothat of target release profile. No significant interaction was found between the drug and the polymer as indicated by DSCand FTIR study. The in vitro drug release followed Korsmeyer and Peppas model kinetics and the drug release mechanismwas found to be of anomalous or non-Fickian type (n = 0.837). Gastroretentive tablets for twice a day dosing could be developedfor clarithromycin.

Onychomycosis is the most common nail disease affecting nail plate and nail bed. Onychomycosis causes onycholysis which creates cavity between the nail plate and nail bed, where drug formulations could be applied, providing a direct contact of drug with the nail bed facilitating drug delivery on the infected area. The purpose of the present study was to design and evaluate the potential of microemulsion-based gel as colloidal carrier for itraconazole for delivery into onycholytic nails for effective treatment of onychomycosis. Itraconazole-loaded microemulsions were prepared and optimized using D-optimal design. The microemulsion containing 6.24 % oil, 36 % Smix, and 57.76 % water was selected as the optimized batch (MEI). The globule size and drug loading of the optimized batch were 48.2 nm and 12.13 mg/ml, respectively. Diffused reflectance FTIR studies were performed to study drug–excipient incompatibility. Ex vivo permeation studies were carried out using bovine hoof and human cadaver skin as models for nail plate and nail bed, respectively. Microemulsion-based itraconazole gel (MBGI) showed better penetration and retention in human skin as well as bovine hoof as compared to commercial preparation (market formulation, MFI). The cumulative amount of itraconazole permeated from the MBGI after 12 h was 73.39 ± 3.55 μg cm−2which was 1.8 times more than MF. MBGI showed significantly higher ex vivo antifungal activity (P < 0.05) against Candida albicansand Trichophyton rubrumwhen compared to MFI. Stability studies showed that MBGI was stable at refrigeration and room temperature for 3 months. It was concluded that drug-loaded gel could be a promising formulation for effective treatment of onychomycosis.Onychomycosis is the most common nail disease affecting nail plate and nail bed. Onychomycosis causes onycholysis which creates cavity between the nail plate and nail bed, where drug formulations could be applied, providing a direct contact of drug with the nail bed facilitating drug delivery on the infected area. The purpose of the present study was to design and evaluate the potential of microemulsion-based gel as colloidal carrier for itraconazole for delivery into onycholytic nails for effective treatment of onychomycosis. Itraconazole-loaded microemulsions were prepared and optimized using D-optimal design. The microemulsion containing 6.24 % oil, 36 % Smix, and 57.76 % water was selected as the optimized batch (MEI). The globule size and drug loading of the optimized batch were 48.2 nm and 12.13 mg/ml, respectively. Diffused reflectance FTIR studies were performed to study drug–excipient incompatibility. Ex vivo permeation studies were carried out using bovine hoof and human cadaver skin as models for nail plate and nail bed, respectively. Microemulsion-based itraconazole gel (MBGI) showed better penetration and retention in human skin as well as bovine hoof as compared to commercial preparation (market formulation, MFI). The cumulative amount of itraconazole permeated from the MBGI after 12 h was 73.39 ± 3.55 μg cm−2which was 1.8 times more than MF. MBGI showed significantly higher ex vivo antifungal activity (P < 0.05) against Candida albicansand Trichophyton rubrumwhen compared to MFI. Stability studies showed that MBGI was stable at refrigeration and room temperature for 3 months. It was concluded that drug-loaded gel could be a promising formulation for effective treatment of onychomycosis.

The aim of proposed research work was to develop a bioadhesive sustained release matrix tablets of zolmitriptan for treatment of migrane. Compression coating technology was used for preparing the tablets that released the drug unidirectionally. Drug loaded core tablets were prepared with mucoadhesive and sustained release polymers like Noveon AA1 Polycarbophil and hydroxypropyl methylcellulose (HPMC K4M) while unloaded coat tablets, that covered the three surfaces of the core tablet, were prepared using ethyl cellulose and Compritol ATO 888. A two factor, three level, face centred, central composite design (CCD) was used to optimize amount of Noveon AA1 and amount of HPMC so as to get required mucoadhesion and rate of drug release. Higher levels of HPMC K4M in the experimental design batches exhibited higher in vitro drug release in the initial hour while the NoveonAA1 levels could be related to increase in mucoadhesive strength. Overlay plot comprising a region that satisfied the constraints for all the selected attributes was generated. Formulation containing 10% w/w of Noveon AA1 and 10% w/w of HPMC K4M was found to be optimum. Checkpoint batches were also prepared to validate the evolved mathematical models. Korsmeyer-Peppas release kinetic model best fitted the optimized batch release profile which showed anomalous diffusion mechanism. The In Vitro drug release could be correlated with the Ex vivo drug permeation. It can be concluded that buccal route can be one of the alternatives available for administration of zolmitriptan.

The purpose of this work was to formulate a controlled release multiple emulsion of carbamazepine favorable for administration in pediatrics and geriatrics suffering from epilepsy, decreasing the dosing frequency, thereby improving patient compliance and providing a platform for personalized medicine. Two–step emulsification procedure was employed for the formulation using liquid paraffin oil, water, surfactants and hydroxypropyl methylcellulose as the stabilizer. 2(4) full factorial design was applied for the optimization of the formulations consistent with the quality by design approach. The response variables were 1st hour release, 5th hour release, and time for 90% drug release and % entrapment efficiency. The optimized batch formulated with 8% w/w Span 60, 3% w/w Tween 80, 0.5% w/v hydroxypropyl methylcellulose (in internal aqueous phase) and the phase volume ratio of 1:1:2 was found to exhibit entrapment efficiency of 70% and zero order release profile. The similarity factor of 71 was obtained on release profile comparison of the 200mg/10ml optimized batch and the marketed Tegretal XR® 200 mg tablets. Carbamazepine being an autoinducer has high half life during the initiation of therapy which decreases during the course of maintenance therapy which requires the dose to be increased. The release profile of 100mg/5ml emulsion and 200mg/10ml emulsion both sufficed the criteria for 30% drug release in 1st hour and prolonged drug release up to 10 and 12 hours respectively. Hence through this research, personalization of therapy was claimed, to titrate the dosing needs according to the individual requirements during the initiation and maintenance therapy.

The present study was aimed towards development of porosity controlled osmotic pump as a platform technology for delivering highly water soluble drugs using Milnacipran HCl as a model drug. Theoretical zero order drug release profile (5 mg/hr) was targeted to achieve for fulfilling desired plasma concentration up to 24 hrs. Novel ethyl cellulose based coating system, Aquarius EKX 19102 SRX-2, was employed in the development of osmotic pump. Influences of media pH, agitation intensity and osmotic pressure on drug release rate were investigated. Statistical approaches including mean dissolution time, dissolution efficiency, similarity factor and SeDeM diagram were applied to translate dissolution profile in to a single value. The Aquarius EKX 19102 SRX-2 coating system at 7% weight gain exhibited zero order drug release. Scanning electron microscopy confirmed the microporous structure of the film. The results obtained from stability study, Fourier Transform Infra Red spectra and Differential Scanning Calorimetry study of optimized formulation confirmed stable characteristics. This platform technology was further validated using Diltiazem HCl and satisfactory results were obtained. FORTRAN language based software was applied to assess drug release kinetics and it was found to be zero order.