Release Retarding Polymer Research Articles

Development of raft-forming liquid and chewable tablet formulations incorporating quercetin solid dispersions for treatment of gastric ulcers

Gastroretentive raft-forming formulations were developed in liquid and chewable tablet dosage forms to achieve prolonged delivery of quercetin in the stomach. The formulations contained a solid dispersion of quercetin and polyvinylpyrrolidone (PVP K 30) at a 1:10 w/w ratio to improve the solubility of the flavonoid. The formulations also contained sodium alginate as a gel forming agent, calcium carbonate as a calcium source and carbon dioxide producer and hydroxypropyl methylcellulose K100M as a drug release retarding polymer. The chewable tablets incorporated mannitol as a diluent. Both liquid and chewable tablet formulations exhibited rapid floating behaviour (lag time < 1 min) and long floating duration (>24 h) in 0.1 N HCl. The optimized liquid formulation showed superior characteristics based on high raft strength (10.4 g) and sustained release of quercetin (93 % over 8 h) whereas the optimized chewable tablet formulation exhibited lower raft strength (7.2 g) and lower drug release (79 % in 8 h). The optimized liquid and chewable tablet formulations were found to induce anti-inflammatory activity in cell culture using RAW 264.7 cells macrophages and enhance the migration of human gastric adenocarcinoma (AGS) epithelial cells in vitro, indicating wound healing potential for treatment of gastric ulcers.

FORMULATION AND EVALUATION OF SUSTAINED-RELEASE PELLETS OF LORNOXICAM

Objective: The aim of the study was to develop sustained release pellets of lornoxicam using Eudragit RLPO and Eudragit RSPO to reduce the dosing frequency.&#x0D; Methods: The sustained release pellets of lornoxicam were prepared by extrusion–spheronization technique using Eudragit RLPO and Eudragit RSPO as release retardant polymers and microcrystalline cellulose as spheronizing agent. A 32 Full factorial design was applied to investigate the combined effect of the two independent variables i.e. concentration of Eudragit RLPO (X1) and concentration of Eudragit RSPO (X2) on the dependent variables, In vitro drug release at 1h (Y1), In vitro drug release at 4 h (Y2) and In vitro drug release at 12 h. (Y3).&#x0D; Results: The optimized formulation (F0) show in vitro drug release 11.24±1.21 %, 43.69±1.28 %, 82.69±1.74 % and 100.24±1.56 % at 1 h, 4 h, 12 h and 24 h respectively. Drug excipients compatibility study by FTIR showed no interaction between drug and excipients. Eudragit RLPO and Eudragit RSPO had a significant effect on in vitro drug release.&#x0D; Conclusion: From all parameters and experimental design evaluation, it was concluded that the drug release rate decreased with an increase the concentration of Eudragit RLPO and Eudragit RSPO. SEM Photomicrograph of pellets revealed that the surface was rough and the pellets were spherical shaped in nature. The in vitro release kinetics revealed higuchi model is followed and drug release is by anamolous diffusion.

Design, development and optimization of sustained release floating, bioadhesive and swellable matrix tablet of ranitidine hydrochloride.

Ranitidine HCl, a selective, competitive histamine H2-receptor antagonist with a short biological half-life, low bioavailability and narrow absorption window, is an ideal candidate for gastro-retentive drug delivery system (GRDDS). Controlled release with an optimum retentive formulation in the upper stomach would be an ideal formulation for this drug. The aim of the present study was therefore to develop, formulate and optimize floating, bioadhesive, and swellable matrix tablets of ranitidine HCl. The matrix tablets were prepared using a combination of hydroxypropyl methylcellulose (HPMC) and sodium carboxymethyl cellulose (NaCMC) as release retarding polymers, sodium bicarbonate (NaHCO3) as gas generating agent and microcrystalline cellulose (MCC) as direct compression diluent. Central composite design (CCD) was used to optimize the formulation and a total of thirteen formulations were prepared. Concentration of HPMC/NaCMC (3:1) (X1) and NaHCO3 (X2) were selected as independent variables; and floating lag time (Y1), bioadhesive strength (Y2), swelling index at 12 h (Y3), cumulative drug release at 1 h (Y4), time to 50% drug release (t50%) (Y5) and cumulative drug release at 12 h (Y6) were taken as the response variables. The optimized batch showed floating lag time of 5.09 sec, bioadhesive strength of 29.69 g, swelling index of 315.04% at 12 h, t50% of 3.86 h and drug release of 24.21% and 93.65% at 1h and 12 h, respectively, with anomalous release mechanism. The results indicate that sustained release matrix tablet of ranitidine HCl with combined floating, bioadhesive and swelling gastro-retentive properties can be considered as a strategy to overcome the low bioavailability and in vivo variation associated with the conventional ranitidine HCl tablet.

Role of Aminated derivatives of Natural Gum in Release Modulating Matrix Systems of Losartan Potassium: Optimization of Formulation using Box-Behnken Design

The aim of the present research work was to systemically device a model of factors that would yield an optimized release modulating dosage form of an anti-hypertensive agent, losartan potassium, using response surface methodology by employing a 3-factor, 3-level Box-Behnken statistical design. Independent variables studied were the amount of the release retardant polymers – aminated fenugreek gum (X1), aminated tamarind gum (X2) and aminated xanthan gum (X3). The dependent variables were the burst release in 15 min (Y1), cumulative percentage release of drug after 60 min (Y2) and hardness (Y3) of the tablets with constraints on the Y2 = 31–35%. Statistical validity of the polynomials was established. In vitro release and swelling studies were carried out for the optimized formulation and the data were fitted to kinetic equations. The polynomial mathematical relationship obtained Y2=32.91-2.29X1-5.68X2-0.97X3+0.20X1X3-0.005X2X3-0.92X12-1.89X22 explained the main and quadratic effects, and the interactions of factors influencing the drug release from matrix tablets. The adjusted (0.9842) and predicted values (0.9600) of r2 for Y2 were in close agreement. Validation of the optimization study indicated high degree of prognostic ability of response surface methodology. The Box-Behnken experimental design facilitated the formulation and optimization of release modulating matrix systems of losartan potassium.

Formulate and evaluate once daily sustained release tablet of highly soluble drug of metformin HCL

The aim of the present study was to design an oral sustained release matrix tablet of highly water soluble biguanide anti diabetic drug. The matrix tablets are prepared by melt granulation method using HPMC K 200M as hydrophilic drug release retarding polymer, and stearic acid as melt able binder as well as hydrophobic carrier. The drug and excipients compatibility was studied by FT – IR. The formulated matrix tablets were characterized for physical parameters and in vitro dissolution profile. FT – IR spectra revealed the absence of drug excipients interaction. The physical parameters of the tablets were found within the limits. The drug release kinetics demonstrated that by increasing the concentration of hydrophilic polymer and hydrophobic carrier the drug release rate was retarded proportionally. Kinetic modelling of in vitro release profile revealing that the drug release from the matrix tablets following first order kinetics, and the drug release mechanism of optimized (F7) formula following non fickian transport mechanism. Accelerated stability studies were performed according to ICH guide lines. Temperature 40±20 c and relative humidity 75±5% RH to study physical and chemical changes of formulation. No physical or chemical changes were observed after t accelerated stability studies.

Study of Release-Retardant Polymers in Formulation Development of Cinnarizine-HCl Sustained-release Oral Suspension Using Raft Technology

The main objective of this research was to develop a sustained-release suspension of cinnarizine hydrochloride using raft-forming technique. This innovative approach has been utilized to formulate a series of suspension formulations using hydroxypropyl cellulose (HPC) as a release-retardant polymeric agent. Cinnarizine sustained-release suspensions were prepared by physical mixing method with varying concentrations and combinations of HPC, sodium citrate, sodium saccharin, calcium carbonate, sodium alginate, methyl hydroxybenzoate and propyl hydroxybenzoate. The formulations were subjected for determination of floating time, floating lag time, weight of the raft, physical appearance and in-vitro dissolution. The dissolution was conducted through USP apparatus 2 (paddle type) in 0.1N hydrochloric acid medium having pH 1.2. The key findings of the study demonstrate that a stable sustained-release suspension of cinnarizine can be formulated using raft-forming approach for increased bioavailability and patient-convenience.&#x0D; Dhaka Univ. J. Pharm. Sci. 19(1): 15-24, 2020 (June)

Venlafaxine Hydrochloride Controlled Release Bilayer Tablets: Optimization of Formulation Variable by Using Dyspnea on Exertion

The current research work was to develop bilayer tablet of venlafaxine hydrochloride to increase drug efficacy for efficient treatment of depression. The satisfactory result of treatment can be achieved upon the maintenance of drug concentration within an effective level in the body, so a uniform and constant drug supply are desirable. An immediate layer of venlafaxine HCl was formulated using super disintegrants, i.e., croscarmellose sodium (CCS) and sodium starch glycolate (SSG); tablet compact by direct compression. HPMC K100M and ethylcellulose (EC) were utilized as release retarding polymers in sustained release layer by wet granulation technique with the help of PVP K30 in IPA solution (10%) as a granulating agent. Full 32 factorial designs were used to find out the optimum quantity of release retardant polymers. Bilayer tablet was evaluated for various parameters, i.e. hardness, friability, weight variation, % drug content, disintegration time (IR layer), and % drug release study. Statically, an analysis was carried out using factor X1 (HPMC K100M) and X2 (EC) for dependent variable % drug release at 8, 12, and 20 hours. A formulation was optimized and a formulation containing 305.36 mg of HPMC K100M and 54.03 mg of ethyl cellulose. Optimized formulation show 47.12 ± 2.1, 59.89 ± 2.2, and 89.06 ± 2.3 drug release at 8, 12, and 20 hours, respectively, which is almost similar to theoretical dose calculation with similarity factor f2 97, 99, and 98%, respectively. Bilayer tablet formulation was observed to be stable and fulfilled all compendia specifications.

Cross-Linked Chitosan Based Stomach Specific Mucoadhesive Microspheres Loaded with Amoxicillin: Preparation and ex vivo Characterization

Objectives: This research was aimed to evaluate a novel approach for preparation of mucoadhesive microspheres which can reside in the gastrointestinal tract for an extended time period. The microspheres contained amoxicillin, an anti-bacterial agent useful for the eradication of Helicobacter pylori. Methods: Ten different formulations were prepared by chemical cross-linking technique using gluteraldehyde as a cross linking agent and chitosan as mucoadhesive polymer. Natural release retardant polymers like guar gum, gum ghatti and xanthan gum were employed. All the microspheres were characterized for morphology, particle size, drug entrapment efficiency, swelling index, bioadhesion to mucosal tissue and in vitro drug dissolution and anti-bacterial activity against E. coli. Results: The FTIR and DSC data indicated that there were no interactions between the drug and polymers used. All the microspheres exhibited good flow properties. The microspheres had a spherical shape with rough surface. The microspheres showed a good mucoadhesivity and also anti-bacterial activity. The release of the drug was prolonged to 12h when incorporated into mucoadhesivemicrospheres. Conclusion: Data obtained in this study concluded that mucoadhesive microspheres of amoxicillin can be used to effectively clear H. pylori from the gastrointestinal tract due to prolonged residence time resulting from mucoadhesion. In this study drug release was diffusion controlled and followed zero order kinetics.

Formulation and In vitro Evaluation of Sustained Release Matrix Tablet of Azathioprine

The main aim of present work was to formulate and evaluate sustain release matrix tablets of Azathioprine, an Antirheumatic Agents. Sustain release formulation are those which delivers the drug locally or systemically at a predetermined rate for a fixed period of time. The matrix tablet was prepared by direct compression method using by various concentration of Ethyl cellulose, Sodium Alginate and HPMC K4M various release retardant polymer. The powder mixtures were subjected to various pre-compression parameters such as angle of repose, bulk density, tapped density and Carr's index shows satisfactory result and the compressed tablets are evaluated for post-compression parameters such as weight variation, thickness, hardness, friability, drug content, In-vitro dissolution studies. In-vitro dissolution studies were carried out for 12 hours using 0.1 N HCL for first 2 hours and pH 6.8 phosphate buffer for 12 hours and the result showed that formulations A7 showed good dissolution profile to control the drug release respectively. Formulation containing higher concentration of HPMC K4M polymer sustained the drug release for the period of 12 hours. The kinetics studies the optimized formulation followed Peppas release kinetics.

Design and optimization of hydrodynamically balanced oral in-situ gel of lamotrigine

In-situ gel formulations were prepared by using different concentrations of sodium alginate, calcium carbonate, trisodium citrate and release retardant polymers. pH triggered ionic gelation is the mechanism involved in the present study. Taguchi L9 OA experimental design was employed for the optimization of formulations. All the formulations were subjected to various evaluation parameters. Taguchi formulations F2 and F6 were found to release the drug for up to 7 hrs hence these formulations were optimized. The formulations were found to follow First order drug release kinetics, the drug release mechanism for both formulations were found to be follow Korsemayer peppas drug release mechanism. From the values of release component “n” it can be concluded that both formulations have fickian diffusional release mechanism. Gastroretentive X-ray imaging study on Albino rabbit demonstrated that it was able to float in the stomach for more than 4hrs. The hydrodynamically balanced oral in-situ gel of lamotrigine could be an effective dosage form which remains buoyant and overcome the cyclical effects of the conventional tablets and sustain the drug release for up to 7 hrs.

Multistage release matrices for potential antiplatelet therapy: Assessing the impact of polymers and Sorb-Cel M® on floating, swelling, and release behavior

BackgroundDual antiplatelet therapy causes gastric bleeding and requires incorporation of gastro protective agent. Objectives: Formulation and invitro evaluation of multistage release bilayer tablets containing three active ingredients (clopidogrel, aspirin & ranitidine) for site specific release i.e. stomach & duodenum. Method: Here, immediate release layer of multistage release matrices contains clopidogrel bisulphate granules and enteric coated aspirin pellets. Second layer is gastro retentive floating layer of ranitidine hydrochloride and developed by using HPMC K100 or xanthan gum as release retarding polymer along with Sorb-Cel M® for the very first time as floating agent. Results: Floating lag time, layer separation time, total floating time and swelling of floating layer increased with increasing concentration of polymer and decreasing concentration of Sorb-Cel M®. FTIR and DSC studies indicated absence of drug polymer interaction while XRD indicated amorphous nature of drugs. Cross section electron micrograph of optimized tablets confirmed our idea, showing stable interface between two layers and intact aspirin pellets in immediate layer. During drug release we demonstrated targeted release of three ingredients at their desired site i.e. clopidogrel and ranitidine HCl at pH 1.2 and aspirin at pH 6.8 to avoid its gastric irritating effect. In floating layer xanthan gum provided better controlled release of ranitidine HCl than HPMC K100. Conclusion: So, concisely our developed matrices could potentially delivers three active pharmaceutical ingredients (APIs) at desired site of action combined in single unit. It will not only reduce pill burden on patients but can also overcome the side effects of concomitant administration of aspirin and clopidogrel bisulphate.

Formulation and In vitro Evaluation of Gastroretentive Floating Bioadhesive Tablets of Nizatidine using Factorial Design

Background: The aim of the present study was to formulate and evaluate floating bioadhesive tablets of Nizatidine which is a competitive, reversible H2-receptor antagonist. Floatingbioadhesive drug delivery system exhibiting a unique combination of floatation and bioadhesion to prolong gastric residence time was prepared. Methods: Polymers used were Hydroxy Propyl Methyl Cellulose (HPMC) K15M as matrix forming water swellable release retarding polymer and carbopol 934P as bioadhesive polymer. The gas generating agents used were sodium bicarbonate and citric acid. The prepared floating bioadhesive tablets of Nizatidine were optimized by 32 factorial design to study independent variable X1 (concentration of CP 934P) and X2 (concentration of HPMC K15M) and dependent variables as floating lag time, cumulative percentage drug release at 12h and swelling index. Tablets were evaluated for various parameters such as hardness, friability, drug content, swelling behavior, floating lag time, bioadhesive strength, drug release profile and stability. Results: All the formulations passed the test for weight variation, hardness, content uniformity and showed acceptable results with respect to drug content (97.93 ± 0.57) and % friability. The tablet containing 25% HPMC K15M and 13.75 % Carbopol 934P was selected as optimized formulation which showed the floating lag time of 74.34±2.08 seconds, drug release of 97.03±0.55% at 12 h (R12h,%), S.I as 79.24±0.87 at 9 h and bioadhesive strength as 10.0023±21.47 g. Stability of the formulation was proved using stability study. Conclusion: The formulated tablets have a potential for controlled release of the drug through floatation and bioadhesion.

Formulation Development and Evaluation of Diacerein Loaded Microsphere by Spray Coating (Wurster Method)

Diacerein loaded microspheres were prepared by spray coating(wurster method) using hydroxyl propyl methyl cellulose (HPMC) and ethyl cellulose as release retarding polymer with a view to manufacture sustained release drug delivery. Drug content in the microspheres was determined by HPLC assay followed by drug entrapment efficiency. Shape and Surface topography of Diacerein loaded microspheres was determined by scanning electron microscopy. Fourier transform infrared spectroscopy (.FT-IR), X-ray diffraction Spectroscopy (XRD), and Differential scanning calorimetry (DSC) studies were done to establish drug polymer and other excipients compatibility and stability. Sustained release action was established by In-vitro release study. The result shows that Diacerein loaded microsphere using hydroxyl propyl methyl cellulose and ethyl cellulose polymer can be a new addition in the field of pain management for the treatment of osteoarthritis. Keywords: Microsphere, Diacerein, HPMC, Ethyl cellulose, Spray coating.

Probing the effect of various lipids and polymer blends on clopidogrel encapsulated floating microcarriers.

Clopidogrel (CLOP) is an antiplatelet drug with poor solubility in intestinal fluid, which limits its bioavailability after oral administration. Current study focuses on developing site-specific floating microcarriers of CLOP using solvent diffusion evaporation method (SDEM) for retaining the drug in the stomach, thus improving the solubility of drug for better absorption. SDEM was employed to formulate floating microcarriers using lipidic excipients, namely Gelucires (GL) to impart floating properties, in combination with ethyl cellulose as release retarding polymer. Prepared particles were 169 ± 6μm to 375 ± 13μm in size, whilst encapsulation efficiency was ranged from 39.6 ± 0.60% to 96.50 ± 3.50%. Electron micrographs depicted discrete spherical microcarriers with porous structure, which amplified with increasing HLB value of GL and concentration of Eudragit E100. FTIR study confirmed absence of major drug polymer interactions while DSC and XRD studies revealed the presence of non-crystalline nature of drug in all formulations. Drug release at pH1.2 enhanced more than 2-folds with increasing HLB value with 32% cumulative drug release for GL 43/01 and 69% for GL 50/13. More interestingly, adding various proportions of Eudragit E100 to GL 43/01 based formulations resulted in increased drug release as high as 71%. In all formulations, the drug release followed diffusion dependent process. It is envisaged that this formulation strategy for CLOP is promising and could possibly be tested in future for its in vivo performance. Graphical abstract Lipid based floating microcarriers of clopidogrel.

Formulation and Evaluation of Gastroretentive Floating Dosage Forms of Clarithromycin

The objective of the present investigation is to formulate gastro retentive floating drug delivery systems (GRFDDS) of clarithromycin for the treatment of Helicobacter pylori, to prolong the gastric residence time after oral administration, at a particular site and controlling the release of drug especially useful for achieving controlled plasma level as well as improving bioavailability and to study the effect of formulation variables on floating lag time, t50 (time required to release 50% of the drug) and t90 (time required to release 90% of the drug). The GRFDDS contains hydroxypropyl methylcellulose (HPMC) and hydroxyl propyl cellulose (HPC) as a release retarding polymer. The concentration of sodium bicarbonate (NaHCo3) was optimized. The tablets were prepared by wet granulation method. The prepared tablets were evaluated for all their physicochemical properties, in vitro buoyancy, drug release and rate order kinetics. From the results, FHM4 was selected as an optimized formulation based on their 12 hrs drug release, minimal floating lag time and maximum total floating time. The optimized formulation followed first order rate kinetics with erosion mechanism. The optimized formulation was characterized with FTIR studies and no interaction between the drug and the polymers were observed.

Formulation and In Vitro Evaluation of Bilayered Matrix Tablets of Pioglitazone for Immediate Release and Glimepiride for Extended Release

Bi-layer tablets are novel drug delivery systems where a combination of two or more drugs in a single unit having different release profiles which improves patient compliance and prolongs the drug action. The study was performed to design bilayer matrix tablets of pioglitazone for immediate release and glimepiride for extended release delivery system. Bilayered matrix tablets composed of two layers, one is immediate release and a second layer is extended release layers. The immediate release layer comprised sodium starch glycolate, and croscarmellose sodium as super disintegrates and extended release layer comprised ethyl cellulose and HPMC K4M as release retardant polymers. Direct compression method was employed for the formulation of bilayer tablets. In vitro studies have shown more than 80% of pioglitazone was released within 60 min. Ethyl cellulose and HPMC K4M retarded the release of glimepiride from the controlled release layer for 12 h. Drug release mechanism exponent (n) was determined for all formulations (0.689-0.789). The release of pioglitazone was found to follow a first order release and the release of glimepiride was followed zero order release model.

Preparation and in vitro &amp; in vivo evaluation of cephalexin matrix tablets

The purpose of the study is to develop cephalexin controlled-release matrix tablets by using lower proportions of release retardant polymer and to establish their in vitro & in vivo correlation. Tablets were compressed by incorporating polymers in a matrix form along with drug which prolong the drug release. Twelve formulations were prepared by mixing ethyl cellulose (EC) and hydroxypropyl methylcellulose (HPMC) (three different viscosity grades) in various proportions. F-1 to F-4 formulations were prepared by incorporating drug, HPMC K4M and ethyl cellulose in 100 : 5 : 5, 100 : 10 : 5, 100 : 15 : 5 and 100 : 20 : 5; similarly, F-5 to F-8 were prepared with HPMC K15M; and F-9 to F-12 were prepared with HPMC K100M using a wet granulation process maintained same proportions, along with drug and EC. Tablets were evaluated for their pre-compression and post-compression characteristics and they were found to be in limits. From the dissolution testing, F-4 showed 100.34% medicament release in 12 h. In vivo studies were conducted on rabbit and pharmacokinetic parameters of the optimized formulation were evaluated using HPLC method. It was found that matrix tablets showed increased t1/2 and decreased Kel. The design signified that the drug release rate from tablets was influenced by the small proportion (around 7% of a tablet weight) of polymer mixture and it controlled 100% medicament release upto 12 h effectively with the low grade viscosity of HPMC combination, with good in vitro & in vivo correlation.

Design and Evaluation of Ion Activated In-Situ Ophthalmic Gel of Brimonidine Tartarate Using Kappa Carrageenan

The objective of the study was to develop optimized formulation of In-situ gel of Brimonidine tartarate (BT), anti-glaucoma agent using Ion activated polymer; Gelrite as gelling agent, kappa carrageenan as mucoadhesive agent and Hydroxy Propyl Methyl Cellulose (HPMC E50) as release retardant polymer. The 23 factorial design was employed to optimize the formulation considering concentration of Gelrite, kappa carrageenan and Hydroxy Propyl Methyl Cellulose as independent variables, mucoadhesive force (N). Viscosity (cP) and In-vitro percentage drug release as dependent variables. Based on mucoadhesive force (N), Viscosity(CPS) and In-vitro percentage drug release, formulation containing concentration Gelrite (0.39%), kappa carrageenan (0.21%) and HPMC E50 (0.4%) was found to be optimized formulation developed by23 factorial design. Formulation was prepared successfully and assessed for gelling capacity, pH, rheological studies,refractive index, optical clarity, isotonicity and as ocular irriation by hen’s egg chorioallantoic membrane (HET-CAM) Test. The overall results of this study revealed that the Brimonidine tartarate/kappa carrageenan in-situ system can be used to enhance ocular retention time.

FORMULATION AND EVALUATION OF NOVEL IN SITU GEL OF LAFUTIDINE FOR GASTRO RETENTIVE DRUG DELIVERY

Objective: The aim of the present study was to formulate and evaluate the novel in situ gel of lafutidine for gastroretentive drug deliveryMethods: A gastroretentive in situ gel of lafutidine was formulated by pH-triggered ionic gelation method using different concentrations of gelling polymer such as sodium alginate, gellan gum, and xanthum gum. Prepared formulations were evaluated for viscosity, density, buoyancy lag time and buoyancy duration, and drug content. In vitro drug release studies of all formulations were also performed. In vivo fluorescence imaging study was conducted for optimized formulation and compared with control.Results: The concentration of gelling agents and release retardant polymers significantly affected viscosity, floating behavior, and in vitro drug release of the formulations. The pH and drug content were found in the range of 6.72–7.20 and 88.74–95.33%, respectively. Floating lag time was &lt;2 min; duration of floating was more than 12 h. Minimum and maximum in vitro drug release were found to be for formulation F9 (51.74%) and F1 (82.76%), respectively, at the end of 12 h. The drug was released from the all the formulations in a sustained manner. In vivo studies confirmed the gastroretention of the formulation in mice stomach for 8 h. Stability studies indicated that the there was no significant change in the visual appearance, floating behavior, and drug content.Conclusion: The gastroretentive in situ gel system, prolonged the gastric residence time, thereby targeting site-specific drug release in the upper gastrointestinal tract.

DEVELOPMENT AND CHARACTERIZATION OF IN SITU GEL OF XANTHAN GUM FOR OPHTHALMIC FORMULATION CONTAINING BRIMONIDINE TARTRATE

Objective: The goal of this study was to develop and characterize an ion-activated in situ gel-forming brimonidine tartrate, solution eye drops containing xanthan gum as a mucoadhesive polymer.Method: Sol-gel formulation was prepared using gellan gum as an ion-activated gel-forming polymer, xanthan gum as mucoadhesive agent, and hydroxypropyl methyl cellulose (HPMC E50LV) as release retardant polymer. Phenylethyl alcohol is used as preservatives in borate buffer. The 23 factorial design was employed to optimize the formulation considering the concentration of gelrite, xanthan gum and HPMC as independent variables, gelation time, gel strength, and mucoadhesive force (N). Gelation time , gel strength, mucoadhesive force (N), viscosity (cP) and in vitro percentage drug release were chosen as dependent variables. The formulation was characteristics for pH, clarity, isotonicity, sterility, rheological behavior, and in vitro drug release, ocular irritation, and ocular visualization.Result: Based on desirability index of responses, the formulation containing a concentration of gelrite (0.4%), xanthan gum (0.21%), and HPMC (HPMC E50 (0.24%) was found to be the optimized formulation concentration developed by 23 factorial design. The solution eye drops resulted in an in situ phase change to gel-state when mixed with simulated tear fluid. The gel formation was also confirmed by viscoelastic measurements. Drug release from the gel followed non-fickian mechanism with 88% of drug released in 10 h, thus increased the residence time of the drug.Conclusion: An in situ gelling system is a valuable alternative to the conventional system with added benefits of sustained drug release which may ultimately result in improved patient compliance.