The present study was aimed to develop a mucoadhesive in situ nasal gel containing domperidone with enhanced drug loading and transnasal permeation properties, which were achieved by improving drug solubility using the concept of mixed solvency. Poloxamer 407 was used as thermosensitive polymer and carbopol 934P as mucoadhesive polymer. Initially solubility of domperidone was enhanced in aqueous solution by using various solubilizers like sodium citrate (SC), urea (UR), polyvinyl pyrrolidone (PVP), polyethylene glycol (PEG), propylene glycol (PG) etc, individually and as a combination of two, three, and four solvents, respectively. Maximum solubility of domperidone was achieved at 30% w/w solvent concentration, containing mixed blend of PVP K30 (7.5% w/w) + PEG 400 (7.5% w/w) + PEG 600 (7.5% w/w) + Propylene Glycol (7.5% w/w), enhancing solubility of domperidone by 172.20 times as compared to its solubility in water. In situ gel was prepared by cold technique. Evaluation of the prepared gel was carried out, including properties like phase transition temperature, viscosity, in vitro drug release, drug content, transnasal permeation and stability studies. In vitro drug release studies of aqueous solution of mixed blend were performed and permeability coefficient was found to be 1.576 × 10 ^-02 cm/hr and flux was found to be 8.64 μg/cm ² hr . Similarly in vitro studies for in situ nasal gel were performed and percent cumulative drug release was 73.05±0.57% in 6 h. Transnasal drug permeation studies results in flux value of 7.04 μg/cm ² hr and percent cumulative drug permeated across the membrane as 86.62±0.992%. The results from stability studies revealed that the prepared thermogel showed no significant decrease in drug content and no physicochemical change was observed upon storage in different temperature conditions resulting as a stable formulation.

The objective of the present study was to investigate the potential of microemulsion formulations for transdermal delivery of indomethacin (IND). Microemulsion formulations with different surfactant:cosurfactant ratios (S_mix ); F1-F6 (1:1, 2:2, 3:1, 4:1, 1:2, and 3:2) were prepared by the spontaneous emulsification method, and characterized for morphology, droplet size, and rheological characteristics. The ex vivo skin permeation studies were performed using Franz diffusion cell with rabbit skin as a permeation membrane. A significant increase in the steady-state flux (J _ss), permeability coefficient (K _p), and enhancement ratio (E _r) was observed in microemulsion formulations compared with the conventional IND gel. The anti-inflammatory effects of microemulsion formulations showed a significant increase in percent edema inhibition value after 4 hours. The optimized formulation showed a significant increase in the steady-state flux (J_ss ) and permeability coefficient (K _p). The enhancement ratio (E_r) was found to be 8.939 in optimized formulation F1 compared with IND gel.

The present investigation highlights the novel trans-buccoadhesive tablets of Famotidine, an H2-receptor antagonist used as an antiulcerative agent. The buccoadhesive tablets were prepared by direct compression method using bioadhesive polymers like sodium alginate, SCMC, HPMC-K100M, PVP-K30 either alone or in combinations with EC as a backing layer. The prepared formulations were evaluated for their physicochemical characteristics, swelling index, surface pH, ex vivo buccoadhesive strength, in vitro, in vivo drug release and ex vivo permeation studies. The distinguishable differences in the results were shown to be dependent on characteristics and composition of bioadhesive materials used. Stability studies were performed in natural human saliva and accelerated conditions showed no significant difference in physical appearance, drug content, buccoadhesive strength and the P-value statistically significant at <0.05. Ex vivo mucous irritation by histological examination reveals, the administration site of buccal tablet over the buccal mucosa did not cause any irritation, ulceration, inflammation and redness, and it resembles to controlled buccal mucosa. Good correlations were observed between in vitro and in vivo drug release, with a correlation coefficient of 0.996. Drug diffusion from buccal tablets showed apparently zero order kinetics and release mechanism was diffusion controlled after considerable swelling.

Bioavailability (BA)/ bioequivalence (BE) studies are the cornerstone for the approval of generic drugs. While BA/BE assessment involving the pharmacokinetic data of the parent compound has been routinely performed, the introduction of the assessment of metabolite(s) data, alone or in addition to parent compound, has also emerged. In this context, the assessment of BA/BE of metabolite(s) may pose additional complexities and challenges, if the metabolic pathway is under the influence of a polymorphic enzyme. This communication provides brief perspectives on the challenges and study design considerations for the assessment of polymorphic metabolite in BA/BE studies.

An extended release tablet provides prolonged periods of drug in plasma levels thereby reduce dosing frequency, improve patient compliance and reduce the dose-related side effects. Ranolazine is indicated for the chronic treatment of angina in patients who have not achieved an adequate response with other anti-anginal agents. The present investigation was undertaken to design extended release tablets of Ranolazine employing hypromellose phthalate grade HP-55, ethocel standard 7FP premium ethyl cellulose, Surelease E-7-19040, Klucel HF pharm and Natrosol Type 250 HHX as matrix forming agents using wet granulation method. Formulated tablets were evaluated for uniformity of weight, assay, water content, in vitro drug release studies and stability studies. The drug release followed first order kinetics with both erosion and diffusion as the release mechanism. It is concluded that the desired drug release pattern can be obtained by using natrosol type 250 HHX compared to other polymers. The similarity factor (f2) was calculated to select best formulation by comparing in vitro dissolution data of the commercial formulation Ranexa^® . The formulated tablets fulfilled the compendia requirements. The formulated Ranolazine Extended release tablets were found to be stable.

Microencapsulation is a unique technique of controlled drug delivery system and is of major importance for effective alteration of drug release required to produce a novel formulation with desired characteristics to overcome the disadvantages of the conventional therapeutic dosage forms. Microcapsules offer efficient absorption and enhanced bioavailability owing to their higher surface area, however, mucoadhesive microcapsules render more intimate contact with the mucus membrane thereby leading to increase in the gastro intestinal residence time. Gliclazide is an oral hypoglycemic second generation sulfonyl urea, which is useful for a long-term treatment of non-insulin dependent diabetes mellitus. In the present investigation, the gliclazide microcapsules are formulated to control the release rate and improve the absorption across gastrointestinal membrane by employing ionic gelation method. The effect of various process variables such as curing time, stirring speed, stirring time, volume and concentration of curing reagent on entrapment efficiency, and drug release rate was studied. The microcapsules were evaluated for drug content, encapsulation efficiency, in vitro drug release studies. The optimized formulation was selected based on the entrapment efficiency and drug release rate. The optimized formulation of gliclazide microcapsules were evaluated for rheological properties, moisture content, swelling index, erosion studies, wall thickness and in vitro wash off test. The microcapsules formulated with 2:1 coat:core ratio by using 150 ml of 0.1M Cacl₂ solution as curing reagent, at a stirring speed of 400 rpm for 60 minutes and a curing period of 48 hrs were found to be the optimum formulation. The drug release followed zero order kinetics and was controlled by peppas mechanism. The pharmacodynamic activity of optimized gliclazide microcapsules was conducted by measuring blood glucose levels in healthy albino rabbits. The percentage glucose reduction was calculated and the data was treated statistically. The hypoglycemic activity was extended up to 10 hours in case of microcapsules.

The aim of the present investigation is to develop and evaluate transdermal patches of nebivolol. The transdermal patches of nebivolol were prepared by solvent evaporation technique. Twelve formulations of nebivolol patches were prepared that composed of ethyl cellulose (EC) with hydroxyl propyl methyl cellulose (HPMC) and ethyl cellulose with polyvinyl pyrrolidine (PVP) in different ratios of 1:2, 1:4, 1:6, 2:1, 4:1, and 6:1 w/w, as film former. Polyvinyl alcohol (4% w/v) was used to prepare the backing membrane. All formulations contained Tween 80 (4% v/w) as penetration enhancer and propylene glycol (40% v/w) as plasticizer in dimethyl formamide as solvent system. The prepared transdermal patches of nebivolol were evaluated for thickness, mass variation, drug content, moisture content, moisture vapor transmission, folding endurance, tensile strength, ex vivo drug permeation study, drug release kinetics, scanning electron microscopy, primary skin irritancy study, and stability study. The physicochemical interactions between nebivolol and different polymers were studied by Fourier Transform Infrared (FTIR). The maximum drug release in 24 h was 95.185% (T2, HPMC:EC is 1:4), which is significant (P < 0.05). Furthermore, the formulation T2 showed maximum skin permeation (13.93 mg/cm ² /h) in comparison with other formulations. The mechanical properties and tensile strength revealed that the formulations were found to be strong enough but not brittle. FTIR studies did not show any evidence of interaction between the drug and the polymers. Nebivolol matrix-type transdermal therapeutic systems could be prepared with the required flux having suitable mechanical properties.

Oral dissolving drug delivery system offers a solution for those patients having difficulty in swallowing tablets/capsules, etc. Zingiber officinale, has been used for medicinal purpose since antiquity to treat motion sickness, pregnancy, and cancer-chemotherapy-induced vomiting, mild stomach upset, cough, chronic bronchial problems, and low-grade infections of all kinds and anorexia condition. This work investigates the possibility of developing Zingiber officinale oral dissolving films allowing fast, reproducible dissolution in oral cavity; thus bypassing first pass metabolism. The oral dissolving films were prepared by solvent-casting method. Prepared films were evaluated for film-forming properties, physico-mechanical properties, palatability, microbial limit test, accelerated stability studies, and clinical efficacy test. The different polymers such as hydroxypropyl methylcellulose 5cps, maltodextrin, pullulan, and polyvinyl alcohol were explored individually and in combination with each other for the formation of film. Among all polymers, maltodextrin and HPMC 5 cps alone and in combination showed excellent film-forming properties as well as very good physico-mechanical properties. The films resulted into excellent palatability along with least disintegrating time. But at accelerated stability studies, only HPMC 5 cps was found to be stable when compared with other formulations. So, it was concluded that HPMC 5 cps is the best film forming as well as stable polymer with respect to Zingiber officinale oral dissolving film.