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In the present research work, Rifabutin, drug used for tuberculosis infection, was encapsulated in lipidic nanoparticles with a view to develop a sustained release oral formulation. The nanocarrier...

Porous silica-based drug delivery systems have shown substantial potential for improving the oral delivery of poorly water-soluble drugs.The major problem with nateglinide, a BCS Class II drug, is pHdependent solubility, limited aqueous solubility, poor dissolution and variable bioavailability. The aim of the present investigation was to develop a lipid-based solid formulation of nateglinide, as a strategy to improve both the solubility and the dissolution rate of the drug in a tablet dosage form. The silica lipid hybrid (SlH) particles were formulated using Miglyol812 and Acrysol el 135 as liquid lipid vehicles as well aslabrasol and Transcutol HP as surfactants.Nateglinide was dissolved in different lipids and later adsorbed on highly porous silica Sylloid PF244 to obtain free-flowing powders. The prepared nateglinide SlH was characterized by FT-IR, DSC, and XRD.Nateglinide SlH was evaluated for solubility and dissolution. SlH of NTG prepared with Miglyol 812 and Transcutol HP enhanced solubility of NTG 57.21 fold. From the study, it may be concluded that the oral solid lipid-based formulation, SlH has an improved potential for enhancing solubility and dissolution of BCS class II drugs like nateglinide.

Objective: Nateglinide is a commonly used oral hypoglycemic, biopharmaceutical classification system Class II drug, which shows relatively poor water solubility and variable bioavailability. The objective of the present investigation was to develop the binary and ternary solid dispersions of nateglinide for improved solubility and dissolution. Methods: Nateglinide solid dispersions were prepared by a common solvent evaporation method. Polymers like soluplus, kolliphor P188, sylloid 244FP, gelucire 48/16, affinisol (HPMCAS), HPβCD, βCD were used in different combinations. The physicochemical characterization of the optimized ternary dispersion was studied by using FT-IR, DSC, and PXRD. Solubility and dissolution behavior of all dispersions were studied. Result: From all prepared ternary solid dispersions, nateglinide dissolution was significantly faster than pure nateglinide. With ternary solid dispersion of NTG, soluplus and kolliphor P188 there was a big improvement in solubility and dissolution. This combination enhanced the solubility of NTG by 23 folds. Another ternary dispersion of NTG with soluplus and gelucire 48/16 enhanced solubility by 25 fold. Conclusion: Ternary solid dispersion found superior over binary dispersions. For the ternary dispersions, showing the best solubility, tablets were prepared. Dissolution and drug release from the formulated tablet was as good as a marketed product.

Introduction: Rifabutin (RFB) is a lipophilic, semi-synthetic antibiotic given for the treatment of atypical mycobacterial infections along with drug susceptible tuberculosis infections. The major challenges in its usage include low oral bioavailability (~20%) mainly due to its low solubility and extensive first pass metabolism. Aim: The present study aims to explore the pharmacokinetics, biodistribution and toxicity of nanocarrier of RFB. Materials and Methods: An experimental animal study was carried out in Institute for Industrial Research and Toxicology, Ghaziabad, Uttar Pradesh, India. RFB nanocarriers were formulated by using solvent diffusion evaporation method with minor modifications and characterised for its physicochemical properties by using various techniques like Field Emission Scanning Electron Microscopy (FESEM), Dynamic Light Scattering (DLS) method, High-Performance Liquid Chromatography (HPLC), X-ray Diffractometry (XRD), in-vitro release study etc. Further nanocarriers were also studied for in-vivo analysis using pharmacokinetics, biodistribution and toxicity studies. GraphPad Prism Software (Version 5.02) was used for the statistical analysis. Results: Nanocarriers of RFB were developed and evaluated for its safety and efficacy. The results of evaluation of nanocarrier for physical and chemical attributes revealed that its particle size obtained was 305-325 nm with low Poly Dispersity Index (PDI) of 0.26-0.36 and the high drug encapsulation efficiency (62.45-70.15%). The nanocarrier formulation showed a sustained release pattern in Simulated Intestinal Fluid (SIF) upto 48 hours and in Physiological Buffer System (PBS) upto 7 days. The in-vivo study showed that the nano-lipoidal drug has significant higher Tmax and Cmax plasma value with higher t1/2(h) values in comparison to plain drug. Moreover, the slow elimination rate (Kel) resulted in significant (p

In the present work attempts have been made to prepare the nanostructured lipid carriers (NLC) gel, by using the poorly water-soluble drug isotretinoin (IT), which is preferably used in the case of acne. The four different formulations of IT-NLC (NLC 1–NLC 4) were prepared using solid and liquid lipid with Tween 80 in different ratios by the hot homogenization method. Properties of entrapment efficiency and drug release behavior were investigated for all formulations from this NLC 4 formulation and optimized. Evaluation of NLC 4 such as particle size, zeta potential, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), transmission electron microscopy (TEM), x-ray diffraction (XRD), and photostabilty study was performed. The nanoparticles were suitably gelled and evaluated for drug content, pH, spreadability, extrudability, rheology, and drug release. Safety to gel was assessed using primary skin irritation studies. The formulated NLC 4 was spherical in shape, with average ...

Background: Azithromycin is an antibiotic, which is preferentially used in the treatment of Mycobacterium Avium Complex (MAC). However, it suffers from drawbacks such as poor solubility, poor bioavailability and adverse effects such as gastrointestinal intolerance, resulting into poor patient compliance. Aim: To develop and optimize lipid based nanocarriers of Azithromycin using QbD approach. Methods: Nanostructured lipid carrier (NLC) were developed by using the solvent diffusion evaporation method with view to release drug in a sustained release manner. The initial factors screening and risk assessment done through Taguchi design and afterwards the optimization of independent factors along with final outcome i.e. critical quality attributes (CQAs) were done by Box Behnken Design (BBD). Results: The results of Physicochemical analysis revealed that a size of optimized Azithromycin Nanocarrier is 346.18 ± 12.90 nm and Polydispersity Index (PDI) of 0.21 ± 0.08; the entrapment efficiency (% EE) of 68.45 ± 4.42% w/w and drug loading of 47.16 ± 0.80 % w/w. The in vitro release study of the Azithromycin Nanocarrier showed a biphasic drug release pattern in simulated intestinal fluid (SIF) nanocarrier shown sustained release kinetics up to 02 days and similar pattern shown in Phosphate buffer saline (PBS) pH 7.4, release kinetics shows initial burst release upto 12 hr followed by sustained release upto 04 days in PBS, pH7.4. The sustained release pattern of the formulation is beneficial to improve the oral bioavailability of the drug. Conclusion: Thus, present research leads to development of formulations which may reduce dose of drug, dosing frequency and enhanced efficaciously of drug. Ultimately it reducing the patient avoidance in treatment.

Objectives In oral absorption of a drug, the drug first dissolves and then is absorbed by diffusion through gastrointestinal membranes. The gastrointestinal environment is aqueous in nature and it is well-known that one-third of the drug population is water insoluble. Hence, there is a need for enhancement of the solubility and dissolution of such drugs. In this work, enhancement of the solubility and dissolution of the practically insoluble drug glipizide was achieved by formation of bionanocomposites (BNCs) using microwave-induced diffusion (MIND), which ultimately leads to bioavailability enhancement. Methods BNCs were formed by using natural carriers such as gelatin, acacia, cassia and ghatti gum, with the help of microwaves. Selection of carriers was based on their surfactant and wetting properties. Solubility studies were carried out to establish the solubility-enhancing property of the BNCs. To support solubility analysis results, dissolution studies (i.e. powder dissolution and in-vitro dissolution) were carried out. The BNCs were characterized by Fourier transform infra-red spectroscopy, differential scanning calorimetry, X-ray diffraction studies, scanning electron microscopy and transmission electron microscopy. In-vivo performance of the optimised formulation was assessed by glucose-induced hyperglycaemia test in male albino Wistar rats. Key findings It was found that as the concentration of polymer in the composite increased the solubility and dissolution of glipizide were enhanced. The optimised ratio (drug : polymer) for all the composites was found to be 1:9. In the glucose-induced hyperglycemia test in rats, the optimized formulation demonstrated a significant reduction in hyperglycemia compared with a marketed formulation, Glynase. Conclusions The novelty of this work is the green and cost-effective way of forming drug nanocomposites with the help of microwave, which can be scaled up to an industrial level. The method gives an immaculate means of solubilisation by generating drug dispersion at the micro and nanoscale level in natural biodegradable stabilising media. Hence, this study demonstrates the use of BNCs in solubility and dissolution enhancement.

The objective of this study was to investigate a novel hydrogel plug using isolated root mucilage of Sterculia urens to obtain a desired lag time for an oral chronotherapeutic colon-specific pulsatile drug delivery of indomethacin. Pulsatile drug delivery was developed using chemically treated hard gelatin capsule bodies filled with eudragit multiparticulates of indomethacin, and sealed with different hydrogel plugs (root mucilage of S. urens, xanthan gum, guar gum, HPMC K4M and combination of maltodextrin with guar gum). Indomethacin multiparticulates were prepared using extrusion spheronization, spray drying and solvent evaporation techniques with Eudragit® L-100 and S-100 (1:2) by varying drug-to-polymer ratio. After oral administration, the water-soluble cap of capsule dissolved in the intestinal fluid and the hydrogel plug swells. After a controlled time, the swollen plug subsequently ejected from the dosage form, releases the contents of the capsule. The formulation factors affecting the drug release were concentration and types of hydrogel plug used. In vivo gamma scintigraphy study in healthy rabbits proved the capability of the system to release drug in lower parts of the gastrointestinal tract after a programmed lag time. This study demonstrates that the indomethacin multiparticulates could be successfully colon-targeted by the design of time and pH-dependent modified chronopharmaceutical formulation. In conclusion, the investigated novel hydrogel plug could be a valuable tool for achieving desired lag time.

This study aims to prepare immediate release glipizide liquisolid tablets using Avicel PH-102 and Aerosil 200 as the carrier and coating material respectively to increase dissolution rate of poorly soluble glipizide. This study also aims to evaluate treated Gellan gum as disintegrant in the preparation of liquisolid tablets. The solubility of glipizide was increased by use of liquisolid technique. The glipizide liquisolid tablets were evaluated for characteristics like drug content, friability, hardness, disintegration time, thermal analysis, X-ray diffraction (XRD) study and dissolution rates. The dissolution patterns of glipizide liquisolid tablets, carried out according to USP paddle method, and were compared with their commercial counterparts. The results obtained shows that all glipizide liquisolid tablets exhibits higher dissolution rates than those of marketed glipizide tablets. Dissolution rates increases with increasing concentration of liquid vehicles and maximum drug release achieved by formulations containing Polyethylene glycol 400 (PEG 400) as a liquid vehicle. The results of XRD and thermal analysis did not show any changes in crystallinity of drug and interaction between glipizide and excipients during the formulation process.

The aim of the present study was to formulate a self-emulsifying drug delivery system of atorvastatin calcium and its characterization including in vitro and in vivo potential. The solubility of atorvastatin calcium was determined in various vehicles such as Captex 355, Captex 355 EP/NF, Ethyl oleate, Capmul MCM, Capmul PG-8, Gelucire 44/14, Tween 80, Tween 20, and PEG 400. Pseudoternary phase diagrams were plotted on the basis of solubility data of drug in various components to evaluate the microemulsification region. Formulation development and screening was carried out based on results obtained from phase diagrams and characteristics of resultant microemulsion. Prepared formulations were tested for microemulsifying properties and evaluated for clarity, precipitation, viscosity determination, drug content and in vitro dissolution. The optimized formulation further evaluated for particle size distribution, zeta potential, stability studies and in vivo potential. In vivo performance of the optimized formulation was evaluated using a Triton-induced hypercholesterolemia model in male Albino Wistar rats. The formulation significantly reduced serum lipid levels as compared with atorvastatin calcium. Thus studies illustrated the potential use for the delivery of hydrophobic drug such as atorvastatin calcium by oral route.

An objective of the present study was to develop alginate/hydroxypropyl methylcellulose (HPMC) based floating-mucoadhesive beads of clarithromycin to provide prolonged contact time of antibiotic to treat stomach ulcer. Floating-mucoadhesive beads were prepared and characterized for in vitro performance followed by investigation of ex vivo study in albino-wistar rats. Beads were prepared by ionic gelation technique where calcium chloride used as gelating agent and incorporated liquid paraffin for floating of the beads. Prepared beads were evaluated extensively for particle size, drug entrapment; swelling and surface morphology by using scanning electron microscopy. X-ray radioimaging study in rabbits, in vitro mucoadhesion using rat stomach mucosal membrane and in vitro drug release studies were carried out. Ex vivo performance of alginate-HPMC beads were studied using albino rats in comparison to simple alginate-calcium beads. Alginate-HPMC beads may be suitable floating-muco-adhesive drug delivery system for delivering clarithromycin to treat stomach ulcers.

Aripiprazole is a novel antipsychotic drug, generally used in schizophrenia and known to act as a partial agonist at D2 and 5 –HT2A receptors. Since stability indicating method is required to discriminate between the intact analyte and degradation products, the present work is aimed at performing purposeful degradation of aripiprazole by exposing it to various pH conditions, oxidative conditions, dry heat and sunlight. Also it describes the final method of analysis of aripiprazole from the tablets. The chromatographic analysis was carried out on HiQSil C8 column (250 X 4.6 mm, 5 µm), mobile phase was Acetonitrile: Potassium Phosphate buffer (pH =3, 100 mM), (40:60 V/V); injection volume 100 µL, detection was carried out at λmax 225nm. Flow rate was 1.0 ml/min. The developed stability indicating method for aripiprazole was validated as per International Conference on Harmonization (ICH) guidelines.

The purpose of the present study was to develop intranasal delivery system of dimenhydrinate using thiolated gellan gum and formulations were modulated so as to have gelation at physiological ion content after intranasal administration. Gelation was determined by physical appearance. The mucoadhesive force in terms of detachment stress, determined using sheep nasal mucosa, increased with increasing concentration of thiolated polymer. The results of in vitro drug permeation studies across sheep nasal mucosa indicate that effective permeation could be significantly increased by using in situ gelling formulation with thiolated polymer concentration. Finally, histopathological examination did not detect any changes during in vitro permeation studies. In conclusion the gel formulation of dimenhydrinate with in situ gelling and mucoadhesive properties with increased permeation rate is promising for prolonging nasal residence time and thereby nasal absorption.

The aim of the present investigation was to develop a pulsatile drug delivery system based on an insoluble capsule body filled with theophylline microspheres and sealed with a swellable novel polymer plug isolated from the endosperm of seeds of higher plant Delonix regia family-Fabaceae. Theophylline microspheres were prepared by solvent evaporation method using Eudragit S 100. The swellable plugs of varying thickness and hardness were prepared by direct compression, which were then placed in the capsule opening. The drug delivery system was designed to deliver the drug at such a time when it was needed most to offer convenience to the chronic patients of asthma. Formulated dosage forms were evaluated for an in vitro drug release study, which showed that the release might be consistent with a release time expected to deliver the drug to the colon depending on the thickness and hardness of the hydrogel plug. Thus, thickness and hardness of the novel polymeric plug plays an important role in controlling the drug release from the formulated drug delivery system.

The objective of this study was to develop a floating, pulsatile, multiparticulate drug delivery system intended for chronopharmacotherapy of arthritis. The floating pulsatile drug delivery has the advantage that a drug can be released in the upper gastrointestinal tract after a definite time period of no drug release, i.e. lag time. Cross-linked beads were prepared using low methoxylated pectin (LM104AS), sodium alginate, and low methoxylated pectin (LM104AS) along with sodium alginate by acid- base reaction during ionotropic gelation. Beads were dried in oven at 50 degrees C for 4 h. Aceclofenac was used as a model drug for encapsulation. Drug loaded multiparticulates were subjected to various characterization and evaluation parameters like entrapment efficiency, surface topography, size analysis and in vitro release study. It was found that calcium pectinate beads show maximum drug entrapment. Hence, pectin containing formulation was further studied for buoyancy, DSC and radio imaging study. Drug release study was performed in acidic environment using pH 1.2 buffer solution for 6 h and then at 7.4 pH for 60 min. The total drug release ranges from 5-10% and 90-94% in acidic and basic media, respectively.

The aim of present investigation was to develop press coated tablet for pulsatile drug delivery of ketoprofen using hydrophilic and hydrophobic polymers. The drug delivery system was designed to deliver the drug at such a time when it could be most needful to patient of rheumatoid arthritis. The press coated tablets containing ketoprofen in the inner core was formulated with an outer shell by different weight ratio of hydrophobic polymer (micronized ethyl cellulose powder) and hydrophilic polymers (glycinemax husk or sodium alginate). The release profile of press coated tablet exhibited a lag time followed by burst release, in which outer shell ruptured into two halves. Authors also investigated factors influencing on lag time such as particle size and viscosity of ethyl cellulose, outer coating weight and paddle rpm. The surface morphology of the tablet was examined by a scanning electron microscopy. Differential scanning calorimeter and Fourier transformed infrared spectroscopy study showed compatibility between ketoprofen and coating material.

Background: Malignant pleural mesothelioma (MPM) is an aggressive tumour originating in the thoracic mesothelium. Prognosis remains poor with 9- to 12-month median survival, and new targets for treatments are desperately needed. Methods: Utilising an RNA interference (RNAi)-based screen of 40 genes overexpressed in tumours, including genes involved in the control of cell cycle, DNA replication and repair, we investigated potential therapeutic targets for MPM. Following in vitro characterisation of the effects of target silencing on MPM cells, candidates were assessed in tumour samples from 154 patients. Results: Gene knockdown in MPM cell lines identified growth inhibition following knockdown of NDC80, CDK1 and PLK1. Target knockdown induced cell-cycle arrest and increased apoptosis. Using small-molecule inhibitors specific for these three proteins also led to growth inhibition of MPM cell lines, and Roscovitine (inhibitor of CDK1) sensitised cells to cisplatin. Protein expression was also measured in tumour samples, with markedly variable levels of CDK1 and PLK1 noted. PLK1 expression in over 10% of cells correlated significantly with a poor prognosis. Conclusion: These results suggest that RNAi-based screening has utility in identifying new targets for MPM, and that inhibition of NDC80, CDK1 and PLK1 may hold promise for treatment of this disease.

Fenofibrate (FBT) is lipophillic drug used in hypercholesterolemia and hypertriglyceridemia having logP 5.375, low solubility (practically insoluble in water) and low oral bioavailability (36%). The purpose of work was to develop FBT nanocrystals for the enhancement of solubility and oral bioavailability. Fenofibrate nanosuspension was prepared using probe sonicator and transformed into dry powder using freeze drying and characterized by DSC, FTIR, XRPD, SEM, particle size, polydispersity index (PDI), zeta potential, solubility, in vitro dissolution, in vivo bioavailability and stability studies. Formulation FNS3 and pure drug exhibited the in vitro dissolution about 73.89% and 8.53% in 1% sodium lauryl sulfate (SLS) media, respectively. When the particle size reduced from 80,000±923nm to 460±20nm, saturation solubility was significantly increased. The saturation solubility of formulation FNS3 in 0.5% and 1% of SLS media found to be 67.51±1.5μg/mL and 107±1.9μg/mL, respectively. While, the saturation solubility of pure drug in 0.5% and 1% of SLS was found to be 6.02±1.51μg/ml and 23.54±1.54μg/ml, respectively. The pharmacokinetic study of optimized nanocrystals (FNS3) conducted in New Zealand white rabbits showed 4.73-fold increase in relative bioavailability than that of pure drug. Long term stability studies showed that there was no significant change in the mean particle size and PDI at 5°C±3°C after 180 days. This enhanced dissolution and bioavailability of fenofibrate nanocrystals could be the promising approach for oral delivery.

A 76 -year-old lady with a recent diagnosis of rheumatic heart disease (RHD), and a history of repeated lower respiratory tract infections, came with symptoms of gastritis unrelated to the primary disease but further diagnostic study in the hospital revealed poorly controlled atrial fibrillation, grossly dilated left atrium with two large left atrial thrombi and mitral valve area1 cm(2). It was decided that the best approach in our patient would be mitral valve replacement with mechanical prosthesis. Despite the usual trend of using bioprosthesis in the elderly, our decision was influenced by the fact that the patient would need chronic anticoagulation for atrial fibrillation in any case. The purpose of our case presentation is to illustrate a late-presenting case of RHD with unusual associations and the challenges to choose the best possible management.

We report a patient who developed multifocal cerebral demyelination with the use of 5-fluorouracil, levamisole, and leucovorin as adjuvant treatment for intestinal adenocarcinoma. The clinical features were acute confusion, restlessness, ataxia, and slurred speech. Magnetic resonance imaging revealed multifocal enhancing white matter lesions. Brain biopsy showed a well-demarcated area of demyelination in cerebral white matter. The patient improved clinically and radiologically after cessation of chemotherapy and a short course of steroids. There have been only 4 previously reported cases of multifocal leukoencephalopathy related to the use of combination 5-fluorouracil and levamisole. The extensive use of these agents as adjuvant treatment for colorectal carcinoma may result in more frequent recognition of this form of neurological toxicity.

Tuberculosis, the infection on the verge of eradication once, is now a great threat to mankind. Emergence of MDR and XDR-TB synergised with HIV and other immune-compressive diseases have increased the life threatening capacities of the disease. A small molecule has been identified here, which showed potent anti-tubercular activity. The identified hit compound has also been proved active against nearly 25 clinical isolates comparable with isoniazid.

The objective of the study is to evaluate the outcome of patients with seronegative spondyloarthritis continuing on sulphasalazine (SSZ) and methotrexate (MTX) after a short course of infliximab. Patients with seronegative spondyloarthritis on MTX and SSZ were given short course of infliximab therapy at 0, 2, 6 and 14 weeks. Outcome of these patients while continuing on MTX and SSZ was assessed. Clinical features, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were noted at baseline (pre-infliximab), 1 month, 3 months and last follow-up after last dose of infliximab infusion. Twenty-four patients were included in this study. The mean duration of follow-up was 9.1 months. Statistically significant reduction in tender and swollen joint count was noted at all the three visits as compared to baseline. Fall in ESR and CRP was statistically significant at 1 and 3 months, but not at last follow-up. Mean reduction in BASDAI at 1 month ,3 month and last follow-up after last infliximab dose were 3.907 (95% CI 2.98–4.83; p < 0.001), 4.53 (95% CI 3.56–5.49; p < 0.001) and 2.48 (95% CI 1.12–3.84; p = 0.002), respectively. Mean reduction in BASFI at 1 month, 3 months and last follow-up after last infliximab dose were 4.13 (95% CI 3.23–5.04; p < 0.001), 4.34 (95% CI 2.8–5.88; p < 0.001) and 2.38 (95% CI 0.86–3.90; p = 0.005), respectively. Continuing SSZ and MTX after short course of infliximab results in sustained improvement in our patients with seronegative spondyloarthritis in India.

In the present investigation, pulsatile release beads were prepared by ionic gelation technique. Theophylline dual-cross-linked beads were prepared by dropping dispersed phase of theophylline, Delonix regia gum (DRG), and sodium alginate into the dispersion phase of different concentration of calcium chloride solution followed by aluminium chloride solution. The formulated beads were further coated by Eudragit L & S 100 in the ratio 1:2 w/w in order to achieve desired lag time. In vitro release study showed lag time of 5–7 h before release of theophylline from the formulated beads, which were found to be intact for 6 h. Thus, formulated dual cross-linked beads when administered at bed time may release theophylline when needed most for chronotherapeutics of early morning asthmatic attacks in chronic patients. In vivo radio imaging study carried out in New Zealand white strain rabbit confirms the findings of in vitro results.

The aim of the present study was to develop theophylline fast release enteric-coated pellets as a pulsatile drug delivery to the colon. The novelty of this work is the combination of pH and time-dependant enteric polymers as a single coating for the development of multiparticulate formulation. Theophylline pellets were optimized by applying a 2-factors 3-levels full factorial design. Continuous dissolution studies were carried out in simulated gastric, intestinal, and colonic fluid with pH 1.2 (0.1 N HCl), pH 7.4 and pH 6.8 (phosphate buffer), respectively. The lag time prior to the drug release was highly affected by combination of two factors, i.e. the percentage of Eudragit RL100 in polymer mixture and coating level. The formulation containing Eudragit RL100 and Eudragit S100 with a ratio of 4:1 and coating level of 12%w/w was found to be optimum. The results of serum study in New Zealand rabbits showed that the developed formulation provided a significant lag phase of 5 h. The present study demonstrates that the theophylline enteric-coated pellets could be successfully colon targeted by the design of pH- and time-dependant modified chronopharmaceutical formulation. In conclusion, pulsatile drug release over a period of 3-12 h is consistent with the requirements for chronopharmaceutical drug delivery.

The purpose of this study was to mask the intensely bitter taste of metoclopramide HCl and to formulate a rapid disintegrating tablet (RDT) of the taste-masked drug. Taste masking was done by complexing metoclopramide HCl with aminoalkyl methacrylate copolymer (Eudragit EPO) in different ratio by the extrusion-precipitation method. Drug-polymer complexes (DPCs) were tested for drug content, in vitro taste in simulated salivary fluid (SSF) of pH 6.8, taste evaluation in oral cavity and molecular property. The complex having drug-polymer ratio of 1 : 2 shows significant taste masking, confirmed by drug release in SSF and in-vivo taste evaluation; therefore, it was selected for further study. Taste evaluation of DPCs in human volunteers revealed considerable taste masking with the degree of bitterness below threshold value (0.5) within 10 s, whereas, metoclopramide HCl was rated intensely bitter with a score of +3 for 10 s. Tablets were evaluated for various parameters like tensile strength, wetting time, water absorption ratio, in-vitro disintegration time, and disintegration in oral cavity. The effect of diluents, lubricants and sweetening agent (Xylisorb) on the disintegration time was also evaluated. Tablets of batch F3 containing mannitol and microcrystalline cellulose in the ratio 1 : 1 and 8% w/w crosspovidone showed faster disintegration (within 20 s) than the marketed formulation (180 s). Good correlation between in vitro disintegration behavior and in the oral cavity was recognized. Tablets of batch F3 also revealed rapid drug release (t(90), 90 s) in SGF compared with marketed formulation (t(90), 600 s).

Gellan gum-based mucoadhesive microspheres of ondansetron hydrochloride for intranasal systemic delivery were prepared to avoid first pass effect, an alternative route of administration to injection and to enhance systemic bioavailability of ondansetron hydrochloride. The microspheres were prepared using spray method. The evaluation results of microspheres were reported in our previous study. The aim of this work was to study the in vivo performance of mucoadhesive microspheres in comparison with oral and intravenous preparations of ondansetron hydrochloride. The nasal delivery system gave increased AUC(0-240) and C(max) as compared to those of oral delivery. In conclusion, the gellan gum-based microsphere formulation of ondansetron hydrochloride with mucoadhesive properties with increased permeation rate is promising for prolonging nasal residence time and thereby nasal absorption.

Intranasal (IN) administration is a promising approach for rapid-onset delivery of medications and to circumvent their first-pass elimination when taken orally. Metoclopramide Hydrochloride (MET HCl) is a potent antiemetic, effective even for preventing emesis induced by cancer chemotherapy. The feasibility of developing an efficacious intranasal formulation of metoclopramide has been undertaken in this study. Formulations were modulated so as to have gelation at physiological ion content after intranasal administration. Gelation was determined by physical appearance. The mucoadhesive force in terms of detachment stress, determined using sheep nasal mucosal membrane, increased with increasing concentration of carbopol. The results of in vitro drug permeation studies across sheep nasal mucosa indicate that effective permeation could be significantly increased by using in situ gelling formulation with carbopol concentration 0.15% or greater. Histological examination did not detect any damage during in vitro permeation studies. Finally, the bioavailability study in rabbits revealed that the absolute bioavailability of MET HCl was significantly increased from 40.67% in the case of the oral drug solution to 54.61% in the case of the nasal in situ gel. This study points to the potential of mucoadhesive nasal in situ gel in terms of ease of administration, accuracy of dosing, prolonged nasal residence and improved drug bioavailability.

The objective of the present study was to prepare ocular inserts of Gatifloxacin. The inserts were fabricated by solvent casting technique, with an aim by achieving once a day administration in the treatment of conjunctivitis. Inserts were evaluated for film thickness, weight variation, drug content, percentage moisture absorption and loss. In-vitro drug release studies were done using bi-chambered donar receiver compartment model. The optimized formulations were subjected to in-vivo studies using rabbits as an animal model and stability studies to assess the effectiveness of the formulations. Finally in-vitro and in-vivo correlation was established. In-vitro drug release data was treated according to zero, first, Korsemeyer Peppas and Higuchi kinetics to access the mechanism of drug release. Formulations were found to be uniform in physicochemical parameter with a fewer variations. Plasticizer was found to influence in mechanical properties as well as modify the drug release rate of the films. Prepared ocular inserts exhibited desired release within 24 h and found to be strongly revealing the efficacy of in vitro-in vivo correlation. From stability studies inserts were remained stable both physically and chemically. No burst effect but a prolonged drug release was observed from all formulations. Thus it achieves target such as increased residence time, prolonged drug release, reduction in frequency of administration and may improve the patient compliance.

The aim of the present study was to develop fast-release enteric-coated tablets for pulsatile drug delivery to the colon. The novelty of this work is a combination of pH- and time-dependant enteric polymers as a single coating. Eudragit S100 was used as a pH-dependant polymer and eudragit RL100 was used as a time-dependant polymer. Theophylline was taken as a model drug. Dissolution studies of enteric-coated tablets were performed with different media having a pH of 1.2, 7.4, and 6.8. Results of the dissolution data show that drug release in the colon could be controlled by using eudragit RL100 eudragit S100. The lag time prior to the drug release was highly affected by a combination of two factors: The percentage of eudragit RL100 and coating level. The optimum formulation was found to be one containing eudragit RL100 and eudragit S100 with a ratio of 60:40 of polymer and coating level of 4.66% w/w. The present study demonstrates that the theophylline enteric-coated tablets could be successfully formulated as a pulsatile drug delivery by the design of a time- and pH-dependant modified chronopharmaceutical formulation. In conclusion, pulsatile drug release over a period of 2-12 hours, consistent with the requirements for chronopharmaceutical drug delivery, can be achieved by using time- and pH-dependant polymers.

Gellan gum microspheres of ondansetron hydrochloride, for intranasal delivery, were prepared to avoid the first pass metabolism as an alternative therapy to parentral, and to improve therapeutic efficiency in treatment of nausea and vomiting. The microspheres were prepared using conventional spray-drying method. The microspheres were evaluated for characteristics like particle size, incorporation efficiency, swelling ability, zeta potential, in-vitro mucoadhesion, thermal analysis, XRD study and in-vitro drug release. Treatment of in-vitro data to different kinetic equations indicated diffusion controlled drug delivery from gellan gum microspheres. The results of DSC and XRD studies revealed molecular amorphous dispersion of ondansetron into the gellan gum microspheres.

The aim of this study was to prepare bi-layer tablet of Metoclopramide Hydrochloride (MTH) and Ibuprofen (IB) for the effective treatment of migraine. MTH and IB were formulated as immediate and sustained release layer respectively. MTH was formulated as immediate release layer by using various disintegrants like Ac-Di-Sol, Polyplasdone XL, Explotab, Agar and Gellan Gum. Treated form of gellan gum and agar was prepared and compared for their disintegrant efficiency with other disintegrants. IB was formulated as sustained release layer using hydrophilic matrix (hydroxypropylmethylcellulose [HPMC K(4)M]). The effect of concentration of hydrophilic matrix (HPMC K(4)M), binder (polyvinylpyrollidone [PVP K(30)]) and buffer (sodium bicarbonate) on IB release was studied. The dissolution study of sustained release layer showed that an increasing amount of HPMC or PVP K(30) results in reduced IB release. The inclusion of buffer (sodium bicarbonate) enhanced the release of IB from sustained release layer. The rational for formulation of bi-layer tablet of these two drugs in combination was (1) MTH increases the absorption of acidic non-steroidal anti-inflammatory drug (NSAID) by increasing gastric motility. So sequential release of MTH (as immediate release) and IB (as sustained release) was suitable for treatment of migraine. (2) MTH was degraded when prolonged contact with acidic NSAID. Bi-layer tablet was suitable for preventing direct contact of these two drugs and thus to maximize the efficacy of combination of two drugs for migraine.

Systemic delivery of drugs via nasal route has many advantages for protein and peptide drug molecules as well as conventional molecules. Mucoadhesive drug delivery systems are those that provide intimate contact of the drug are those that provide intimate contact of the drug with the mucosa for an extended period of time. In this current work chitosan mucoadhesive microspheres of ondansetron HCL were prepared by spray-drying method, with an aim to avoid first pass effect and to improve therapeutic efficacy of Ondansetron in treatment of nauseas and vomiting. Preformulation studies were carried out in order to find out the drug excipient interaction in order to find out the drug excipients. I.R. spectrum and TLC method was used to find out the interaction between drug and excipient. Formulations were evaluated for physical characteristics such as particle size, incorporation efficiency, swelling ability in vitro bioadhesion and in vitro drug release in pH 6.6 phosphate buffer. Average particle size of microspheres was found to be in size of microspheres was found to be in size range 7-9 µm. All microspheres had good percentage of entrapment efficiency between 88% and 97% chitosan microspheres showed very good mucoadhesion due to electrostatic attraction between chitosan and mucin. The Fourier transformed infrared (FTIR) spectra obtained from various formulations of spray-dried microspheres showed no interaction within these formulations. The release of ondansetron hydrochloride from these microspheres was fast. These in vitro results show that spray-dried microspheres based on chitosan could be suitable nasal mucoadhesive delivery system for administration of ondansetron hydrochloride.