The present investigation concerns with the development and optimization of an in situ forming formulation using 3(3) full factorial design experimentation. Metformin, an antidiabetic drug with upper part of gastrointestinal tract as absorption window was used as a model drug. The formulations were designed with an objective to retain in stomach for an extended time period. The effect of three independent factors--concentrations of sodium alginate (X(1)), gellan gum (X(2)), and metformin (X(3)) on in vitro drug release were used to characterize and optimize the formulation. Five dependent variables-release exponent (Y(1)), dissolution efficiency (Y(2)), drug release at 30 min (Y(3)), 210 min (Y(4)), and 480 min (Y(5)) were considered as optimization factors. The data were statistically analyzed using ANOVA, and a p < 0.05 was considered statistically significant. Three dimensional surface response plots were drawn to evaluate the interaction of independent variables on the chosen dependent variables. Of the prepared 27 formulations, the responses exhibited by batch F17 containing medium level sodium alginate (X(1)), low level gellan (X(2)), and medium level metformin (X(3)) were similar to the predicted responses.

Chitosan beads loaded with ciprofloxacin hydrochloride were fabricated by ionic cross-linking with sodium tripolyphosphate. The beads showed an excellent water retention property. The degradation of fabricated beads was influenced by the pH of test medium. High drug load was achieved within the bead with a short curing time. Drug release was high in acidic medium (pH 1.2) vis-à-vis intestinal medium (pH 7.4). Ciprofloxacin hydrochloride release increased with an increasing concentration of ciprofloxacin and decreasing proportion of chitosan. Drug release followed both first-order and Higuchi's root time kinetics showing non-Fickian release mechanism.

Different types of in situ gelling systems of indomethacin, in sodium alginate vehicle, were prepared and evaluated for their pharmaceutical properties including viscosity, sterility and drug content uniformity. The gelling efficacy of the prepared systems was evaluated by using an in house fabricated gelation cell. The in vitro release kinetics of the prepared systems was determined in simulated tear. The gelling time and the nature of the gel formed were dependent on the concentration of sodium alginate present in the systems. The drug release from these systems was extended up to 8 h and predominately followed zero-order kinetics.

In an attempt to fabricate floating beads of ciprofloxacin, drugloaded alginate beads were prepared by simultaneous external and internal gelation. The effect of blending of alginate with gellan, hydroxypropyl methylcellulose, starch, and chitosan on the bead properties were evaluated. Beads were spherical with incorporation efficiency in the range of 52.81 ± 2.64 to 78.95 ± 1.92%. Beads exhibited buoyancy over a period of 7-24 hr based on the formulation variables. In vitro release of ciprofloxacin from the alginate beads in simulated gastric fluid (SGF) (0.1 N HCl, pH 1.2), was influenced significantly (p < 0.001) by the properties and concentration of additives. Among the polymers incorporated into alginate beads. Hydroxy propyl methylcellulose (HPMC) provided an extended release over 7 hr. The drug release predominately followed Higuchi's square root model.

Periodontal pocket inserts of niridazole (NZ) made with Resomer(R) (grades RG 503H and RG858, designated as RH and RG, respectively) were studied. Various formulation variables were evaluated to obtain a biodegradable delivery systems showing device degradation and drug depletion parallel to each other in vitro. Drug release from the prepared inserts was evaluated using a static dissolution setup (for 1 month). Incorporation of 3 parts of RG in 1 part of RH inserts caused a 50% decrease in the initial release rate. The RH-NZ inserts showed a spurt in release around the 10th day of the study, which coincided with the decrease in device weight, suggesting onset of device degradation. Pilot-scale clinical trials in 12 patients indicated improvements in clinical indices from the baseline values. The average pocket depth was reduced significantly (alpha = 0.05) from 6.34 +/- 1.86 mm at baseline to 5.94 +/- 0.28 mm after 28 days of treatment.

Over the last three decades, various approaches have been pursued to increase the retention of an oral dosage form in the stomach, including floating drug delivery systems (FDDS), swelling and expanding systems, bioadhesive systems, modified shape systems, high-density systems and other delayed gastric emptying devices (1). FDDS are widely explored for gastroretention purposes and have a bulk density lower than gastric fluids and thus remain buoyant in the stomach without affecting the gastric emptying rate for a prolonged period of time. While the system is floating on gastric contents, the drug is released slowly at a desired rate from the system (1, 2).Sodium alginate (SA) is a widely used natural polymer in various drug delivery systems. It exhibits favourable biological properties such as non-toxicity, biocompatibility, biodegradability and ulcer healing traits. Moreover, gelation of dilute solutions of SA occurs on addition of di-and trivalent metal ions by a co-operative process involving consecutive G-residues in the a-L-guluronic acid blocks of the alginate chain in a manner described by the 'egg-box' model (3). The procedure by which gelation is achieved is similar to the previously reported in situ gelling formulations of sodium alginate (4, 5).H 2 -antagonists or proton pump inhibitors are clinically used in treating chronic conditions like peptic ulcer and reflux oesophagitis. H 2 -antagonists competitively inhibit his- In the present work, a gastroretentive in situ gelling liquid formulation for controlled delivery of ranitidine was formulated using sodium alginate (low, medium and high viscosity grades), calcium carbonate (source of cations) and ranitidine. Prepared formulations were evaluated for viscosity, buoyancy lag time and buoyancy duration, drug content and in vitro drug release. Formulation variables such as concentration of sodium alginate, calcium carbonate and drug significantly affected the formulation viscosity, floating behavior and in vitro drug release. Analysis of the release pattern showed that the drug release from in situ gel followed a diffusion mechanism.

Abstract. In the present investigation, hydrogenated cottonseed oil (HCSO) was evaluated as a sustained release matrix for a freely soluble drug, tramadol. Hydrophobic matrix tablets of tramadol, was evaluated by compression of physical mixture of drug and wax, dispersion of drug in HCSO by hot fusion or solubilisation techniques. The method of preparation of tablet had a significant effect on drug release with higher release observed from direct compression matrices and slower release from matrix prepared by dispersion (hot-fused matrices). Influence of addition of hydroxypropylmethyl cellulose, sodium carboxymethyl cellulose, polyethylene glycol 4000 and surfactants like sodium lauryl sulphate and polysorbate 20 to HCSO matrix on drug release was investigated. The added excipients exhibited a propensity to enhance drug release from the HCSO matrix. NaCMC was effective at a lower ratio (<10% w/w) and when incorporated at higher level made HCSO matrix to erode and disintegrate in a short period.

Chitosan inserts for periodontitis: Influence of drug loading, plasticizer and crosslinking onin vitrometronidazole releaseChitosan based metronidazole (MZ) inserts were fabricated by the casting method and characterized with respect to mass and thickness uniformity, metronidazole loading andin vitrometronidazole release kinetics. The fabricated inserts exhibited satisfactory physical characteristics. The mass of inserts was in the range of 5.63 ± 0.42 to 6.04 ± 0.89 mg. The thickness ranged from 0.46 ± 0.06 to 0.49 ± 0.08 mm. Metronidazole loading was in the range of 0.98 ± 0.09 to 1.07 ± 0.07 mg except for batch CM3 with MZ loading of 2.01 ± 0.08 mg. The inserts exhibited an initial burst release at the end of 24 h, irrespective of the drug to polymer ratio, plasticizer content or cross-linking. However, further drug release was sustained over the next 6 days. Cross-linking with 10% (m/m) of glutaraldehyde inhibited the burst release by ~30% and increased the mean dissolution time (MDT) from 0.67 to 8.59 days. The decrease in drug release was a result of reduced permeability of chitosan due to cross-linking.