Wet Granulation Technique Research Articles

BILAYER TABLET TENDERED IMMEDIATE RELEASE OF PARACETAMOL AND SUSTAINED RELEASE OF IBUPROFEN FOR QUICK ONSET OF ACTION AGAINST PAIN AND FEVER

Objective: The objective of this research was to formulate bi-layer tablet which contains immediate-release layer of Paracetamol for quick onset of action and sustained release of Ibuprofen for prolonging long period.
 Materials and Methods: The following chemicals were used: Paracetamol (Combiotic Global Pvt. Ltd., India), Ibuprofen (Combiotic Global Pvt. Ltd., India), microcrystalline cellulose (MCC) (Avicel), and Polyvinylpyrrolidone (PVP) K-30 (Loba Chem). Wet granulation method was adapted to formulate the bilayer tablets. The immediate-release layer of Paracetamol was prepared using sodium starch glycolate as superdisintegrants, MCC as diluent, starch as binder. The sustained release layer of Ibuprofen was prepared using high-performance liquid chromatography E50LV and ethyl cellulose as binder along with other excipients such as MCC, PVP, and magnesium stearate by wet granulation technique.
 Result and Discussion: The release rate of Paracetamol from Formulations 1 was more than 80% at 40 min. In case of Ibuprofen, sustained-release polymers such as HPMC E50 LV were used to increase the release time.
 Conclusion: The bilayer tablets were prepared and show good release rate.

Gastroretentive floating matrix tablets of cephradine based on psyllium husk

Sustained-release gastroretentive floating matrix tablets of cephradine were prepared for better patient compliance. Eight different tablets were prepared by using two natural polymers, psyllium husk powder (F1–F4) and xanthan gum (F5–F8), through the wet granulation technique. These tablets were characterized by pre- and postcompression analysis, Fourier transform infrared spectroscopy, swelling index study, in vitro buoyancy and dissolution study. Data were analyzed by model-dependent and model-independent analysis to devise the release mechanisms. The polymers exhibited excellent sustained-release behavior as well as binding characteristics. Pre- and postcompression parameters were observed in the specified official pharmacopoeia range. The drug contents of all the formulations were found in the range 95·52–99·63%. No chemical interaction was found between the drug and polymer. All formulations exhibited a good floating time – that is, >24 h – except F8, which remained buoyant for less than 1 h in simulated gastric fluid (pH 1·2). All of the formulations exhibited a direct relation between the swelling index and viscosity of polymer matrices. The significance of the wet granulation technique was indicated by the polymer action as a binding agent in wetting solution. From comparison of the two polymers, psyllium husk powder efficiently retarded the drug release owing to its high gelatinous swollen mass.

Formulation and In-Vitro Evaluation of Taste Masked Fast Disintegrating Tablets of Labetalol Hydrochloride by Wet Granulation Technique

Labetalol Hydrochloride is a β-blocker generally indicated for the treatment of hypertension, and it is extensively metabolized due to the hepatic metabolism. In the present work, an attempt was made to mask the taste by Solid Dispersion technique, with a formulation into Fast Disintegrating dosage form, using superdisintegrants such as Cross carmellose sodium (CCS), crospovidone (CP) and sodium starch glycolate (SSG). The complexes of Labetalol hydrochloride with HP-β-CD (1:3 ratio) were prepared by Co-precipitation method. Using the drug HP-β-CD complex, Fast Disintegrating tablets were prepared by Wet granulation Technique and evaluated for hardness, friability, weight variation, thickness, disintegrating time (DT), In-vitro dispersion time and dissolution rate. The results of Direct compression optimized formulation WG9 (Sodium Starch Glycolate 15mg and Starch paste 18mg) has shown the % Drug release of 99.97%, In-vitro Dispersion time of 16 Secs respectively. Keywords: Solid dispersions, fast disintegrating tablets, Labetalol, Crospovidone, Croscarmellose sodium and Sodium starch glycolate.

Formulation and Evaluation of Floating Tablets of Sitagliptin with Extract of Triphala

The aim of the present work is to formulate, optimize and evaluate hydrodynamically balanced antidiabetic system incorporated with sitagliptin and phytochemical constituents of Triphala extract for the treatment of constipation associated with diabetes. The Triphala churna of two different ratios, 1:1:1 (TC1) and 1:2:4 (TC2) were subjected to hot percolation using Soxhlet apparatus using methanol as solvent. The floating matrix tablets of Sitagliptin with methanolic Triphala extract was prepared by wet granulation technique using HPMC K4M as polymer, starch/honey as binder and sodium bicarbonate & citric acid as effervescent agents by 24 factorial design. The compatibility studies showed that there is no chemical interaction between the drug, polymer and the excipients used in the tablets. The independent variables are drug & Triphala extract ratio (X1), Triphala proportion (X2), binder used for granulation (X3), and amount of effervescent excipients used (X4). The dependent variables are hardness (Y1), buoyancy lag time (Y2), total floating time (Y3), in-vitro drug release (Y4), and T50% (Y5). The prepared floating tablets were subjected to all post compression parameters such as hardness, friability, swelling capacity, buoyancy, total floating time, drug content & in-vitro drug release and were found to be within normal limits. Based on drug content, buoyancy lag time and in-vitro drug release the formulations F14 and F16 were selected for in-vivo study of the formulation. Keywords: Triphala, Sitagliptin, honey, floating tablet.

ONCE DAILY IMMEDIATE-AND EXTENDED-RELEASE BILAYER TABLETS OF ETORICOXIB: A STUDY ON THE RELEASE KINETICS

Objective: In the present work, the main objective was to develop bilayer extended release matrix tablets of etoricoxib by providing a loading dose followed by maintenance dose that expected to improve the therapeutic efficacy of the medication with less toxic effect.
 Methods: Bilayer tablets of etoricoxib was developed successfully with the meticulous proportion of release controlling Hydroxy propyl methyl cellulose K100 (HPMC K100) and lactose. The tablets were prepared by wet granulation technique. Granules for immediate layer and extended layer for different formulations were prepared separately. The formulations were developed and evaluations were performed to examine the parameters that affect the in vitro performance of the tablets. The drug-excipient compatibility was ensured by Fourier transform infrared spectroscopy (FTIR) study.
 Results: The values of physical parameters of all formulations were found within appreciable limit. Formulation containing HPMC K 100 and lactose in the proportion of 2:1 in the extended release layer was able to release 26.22% of drug in 15 min and shown a steady release of drug for an extended period of 12 h. The dissolution data was put in Korsemeyer–Peppas model in order to find out n value, which describes the drug release mechanism. The n-value of different formulations were found to be variable. The Fourier transform infrared spectroscopy (FTIR) study revealed absence of any other new peaks and also no differences in the positions of the absorption bands in the bilayer tablet F8 that indicate the lack of significant interactions between etoricoxib and other excipients.
 Conclusion: It had been concluded that once daily immediate-and extended release bilayer tablet of etoricoxib can be formulated with profound physical characteristics and dissolution properties. This resulted in reducing the daily dose and thus minimise the cardiovascular toxicity of etoricoxib.

Formulation and Optimization of Omeprezole Floating Tablet by Wet Granulation Technique

Omaprezole is a proton pump inhibitor, antacid drug. It is categorized as class II in BCS system of classification of drugs. Omaprazole inhibits the H(+)-K(-) ATPase in the proton pump of gastric parietal cells and highly effective inhibitor of gastric acid secretion. Floating tablet is nowadays considered as one of the best method to enhance the retention time of tablet in stomach. To get a better dissolution rate, the retention time of Omaprazole is enhanced by the floating technique. The aim of the work is to formulate the floating tablet of Omaprazole and evaluation of tablets invitro performance. The floating tablets are prepared by using two different polymers; HPMC K15, HPMC K100. Wet granulation method was used to prepare tablet. The polymers added in different ratios. The increasing concentration of polymers is responsible for enhancement of drug content and percent yield due to increase in the swallability of polymer.Invitro drug release study was performed using United State Pharmacopoeia (USP) type II dissolution test apparatus employing paddle stirrer at 50 rpm using 900ml of 0.1 N HCL buffer maintained at 37⁰C±0.5⁰C as the dissolution medium. The FTIR, DSC studies of Omaprazole floating tablet indicated the phase inversion of Omaprazole from crystalline to amorphous form. The F3 formulation show increased drug release as compare to pure drug in 24 hrs. It can be concluded that the floating tablet of Omaprazole prepared with mixture of HPMC K15 and HPMC K100 has greater retention time than pure drug and marketed formulation.

FORMULATION AND EVALUATION OF TELMISARTAN FAST DISSOLVING TABLETS USING JACK FRUIT SEED STARCH AS SUPERDISINTEGRANT

Objective: The main objective of the current study is to enhance the solubility of Biopharmaceutical Classification System (BCS) Class-II drug Telmisartan using jack fruit seed starch as super disintegrant which increases drug release.
 Methods: Starches were extracted using alkali technique using sodium hydroxide at 0.1%, 0.25%, and 0.5% concentrations and water from Jack fruit seed powder. These starches were evaluated for various phytochemical and physicochemical tests. Fast dissolving tablets were prepared using Telmisartan, jack fruit seed starch and Croscarmellose sodium in various concentrations using wet granulation technique. Various pre and post-compression parameters were evaluated along with in vitro drug release studies, characterization studies like Fourier Transform Infra-Red spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM), X-Ray Diffraction (XRD) and accelerated stability studies.
 Results: Phytochemical tests revealed the presence of only starch in all the extracts. The starch prepared from 0.1% sodium hydroxide (JFS2) showed best physicochemical properties. From in vitro dissolution studies, it was observed that formulations F5 and F11 containing 15% w/w of JFS2 and 15% w/w of croscarmellose sodium showed faster disintegration and increased dissolution rate compared with other formulations. FTIR and DSC studies showed that there were no major interactions among drug and excipients. XRD studies revealed the nature of formulations. Accelerated stability studies revealed the stability of tablets.
 Conclusion: Thus, the tablets prepared using Jack fruit seed starch revealed the super disintegrant property of starch.

Preparation of novel optimum liquisolid compacts via incorporating water granulation process to enhance the powder characterizations and dissolution behavior of a poorly soluble drug: Norfloxacin

The aim of this work is to investigate the addition of wet granulation technique into liquisolid process in order to enhance the characterizations of liquisolid compacts, such as flowability, compressibility and the percentage of drug release (using norfloxacin as a model of poorly soluble-permeable drug) in neutral dissolution medium. The water in the liquisolid formulations works as a liquid binder to the carrier and coating particles, creating a wider space inside their structure, which allows the amount of the liquid vehicle (PEG200 or Synperonic ™ PE/L-61) to increase inside the formulations. This feature reflects positively on: the flowability (decreasing the angle of the slide up to 10 degrees), the compressibility (increasing the load factor from 0.2 to >0.4 in PEG200 liquisolid compacts and from 0.14 to 0.29 in the case of Synperonic ™ PE/L-61iquisolid compacts) and the dissolution behaviour of norfloxacin (increasing drug release). The applied accelerated stability study on the water granulated liquisolid compacts showed no significant differences in the dissolution profiles. Also, the DSC thermographs indicated that the water granulated liquisolid compacts resist the applied stressful conditions. As a consequence, the positive outcomes of the combination between liquisolid and water granulation process open the door for robust tablet production on a large scale in pharmaceutical industries.

FORMULATION, DEVELOPMENT AND IN VITRO EVALUATION OF TRAMADOL EXTENDED RELEASE TABLETS

Objective: The objective of the present study was to develop “once daily” extended release tablets of tramadol (100 mg) by wet granulation using hydrophilic polymer like hydroxy propyl methyl cellulose K100M,K15M and polyethylene oxide (PEO).
 Methods: The tramadol matrix tablets were prepared by using different polymers like hydroxy propyl methyl cellulose (HPMC K15M and K100M), polyethylene oxide (PEO) as the nontoxic and easily available suitable matrix system. The extended release tablets of tramadol (400 mg) were prepared wet granulation technique. Different pre compression and post compression were performed. In vitro dissolution tests were performed and percentage drug release was calculated. The fourier-transform infrared spectroscopy (FTIR) studies conducted on pure drug tramadol and the optimize formulation (T6). Different release models like zero order, first order, higuchi and Korsemeyer-Peppas were applied to in vitro drug release data in order to evaluate the drug release mechanisms and kinetics.
 Results: Pre compression and post compression parameters satisfied with pharmacopeia specifications. The In vitro release studies were performed using USP type II apparatus showed that optimized formulation T6 consisting of polyethylene oxide (PEO) with 25 mg of the polymer was found to extended release of tramadol over a period of 24h. The optimized formulation T6 followed the zero order kinetics as correlation coefficient (r2) values are higher than that of first-order release kinetics. In order to understand the complex mechanism of drug release from the optimized formulation T6 matrix system, the in vitro release rate were fitted to Korsemeyer-Peppas model and the release exponent value (n) obtained was 0.82105 exhibited anomalous (non fickian) diffusion mechanism.
 Conclusion: The present study shows that polyethylene oxide was found to play a great role in controlling release of tramadol from the matrix system. Accordingly it can be concluded that the formulation is robust in the performance is less likely to be affected by the various factors studied.

FORMULATION AND EVALUATION OF DOLUTEGRAVIR SODIUM SOLID DISPERSIONS AND FAST DISSOLVING TABLETS USING POLOXAMER-188 AND JACK FRUIT SEED STARCH AS EXCIPIENTS

Objective: The current work mainly focuses on solubility enhancement of dolutegravir which is a biopharmaceutical classification system Class-II drug using jack fruit seed starch (JFS2) as excipient which improves the drug release.
 Materials and Methods: Starches were extracted using aqueous and alkali methods (sodium hydroxide at 0.1%, 0.25%, and 0.5% concentrations) from jack fruit seed powder. These starches were evaluated for phytochemical and physicochemical parameters. Fast dissolving tablets were prepared using dolutegravir sodium solid dispersion, JFS2, and croscarmellose sodium (CCS) in various concentrations using wet granulation technique. Various pre- and post-compression parameters were evaluated along with in vitro drug release studies; characterization studies such as Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), scanning electron microscopy, X-ray diffraction (XRD), and stability studies.
 Results: Phytochemical tests revealed the presence of only starch in all extracts. Starch prepared from 0.1% sodium hydroxide (JFS2) showed best physicochemical properties. From in vitro dissolution studies, it was observed that solid dispersion formulation DF3 containing dolutegravir sodium and poloxamer-188 in 1:1.5 ratios showed a better dissolution rate. From in vitro dissolution studies, tablet formulations DFT6 and DFT9 containing 12.5% w/w of JFS2 and 12.5% w/w of CCS showed enhanced dissolution rate compared with other formulations. FTIR and DSC studies revealed that there were no major interactions between drug and excipients. XRD studies revealed the nature of formulations. Accelerated stability studies showed that all tablets were stable.
 Conclusion: The tablets prepared using jack fruit starch seed starch revealed the superdisintegrant property of starch.

Evaluation of the Disintegration Properties of Khaya senegalensis Gum Using Paracetamol Tablets

Background: Disintegrants are essential in the formulation of solid dosage forms such as tablets because they aid in the release of the active drug for therapeutic action. Disintegrating agents such as starch are currently posing challenges such as tablet softening and slow disintegration. In the quest for alternatives that are cheaper, readily available and possessing same or better disintegrating property, Khaya senegalensis gum was considered. Currently, there is no available literature pertaining to its disintegrating property.
 Objective: To investigate the disintegrating properties of Khaya senegalensis gum using paracetamol tablets.
 Methods: K. senegalensis gum was obtained by making an incision on the stem bark of the mahogany tree. The dried purified K. senegalensis gum was employed in the formulation of granule I whiles Tragacanth gum was used in formulating granule II using the wet granulation technique. The flow properties of both granules were subsequently determined and compared. Paracetamol tablets were then produced with the formulated granules I and II. Friability, hardness, weight uniformity and disintegration testing were performed on the paracetamol tablets formulated with both granules.
 Results: The results showed granule I had a better flowability with angle of repose 31.63°C, Hausner’s ratio 1.24 and Carr’s index 19.57 as compared to granule II with angle of repose 34.72°C, Hausner’s ratio 1.31 and Carr’s index 23.84. The study also revealed, paracetamol tablets formulated with granule I (K. senegalensis gum) passed the hardness test (6.57 Kg.f), disintegration time (2.44 min), weight uniformity test (2.2% standard deviation) and friability test (0.69%). Paracetamol tablets formulated with granule II (Tragacanth gum) also passed the hardness test (8.20 Kg.f), disintegration time (7.69 min), weight uniformity test (1.6% standard deviation) and friability test (0.86%).
 Conclusion: Khaya senegalensis gum can therefore be explored as an alternative disintegrant in the formulation of paracetamol tablets for improved bioavailability.

Formulation, optimization, and evaluation of raft-forming formulations containing Nizatidine

Objective: The main objective of this research is to formulate, optimize, and evaluate raft-forming chewable tablets of Nizatidine. Various raft-forming agents were used in preliminary screening. Sodium alginate showed maximum raft strength, so tablets were prepared using sodium alginate as the raft forming agent, along with calcium carbonate (CaCO3) as antacid and raft strengthening agent, and sodium bicarbonate (NaHCO3) as a gas generating agent.Research design and methods: Raft forming chewable tablets containing Nizatidine were prepared by direct compression and wet granulation methods, and evaluated for drug content, acid neutralization capacity, raft strength, and in-vitro drug release in 0.1 N HCl. Box–Behnken design was used for optimization.Results: Two optimized formulations were predicted from the design space. The first optimized recommended concentrations of the independent variables were predicted to be X1 = 275.92 mg, X2 = 28.60 mg, and X3 = 202.14 mg for direct compression technique and the second optimized recommended concentrations were predicted to be X1 = 253.62 mg, X2 = 24.60 mg, and X3 = 201.77 mg for wet granulation technique. Optimized formulations were stable at accelerated environmental testing for six months at 35 °C and 45 °C with 75% relative humidity. X-Ray showed that the raft floated immediately after ingestion and remained intact for ∼3 h.Conclusion: Raft was successfully formed and optimized. Upon chewing tablets, a raft is formed on stomach content. That results in rapid relief of acid burning symptoms and delivering the drug into systemic circulation with enhanced bioavailability.

Formulation and Comparative Evaluation of Etoricoxib Loaded Osmotic Drug Delivery Systems

Osmotic drug delivery systems are gaining interest as they deliver the drug based on the principle of osmosis. Osmosis is defined as the spontaneous movement of solvent from a solution of lower solute concentration to a solution of higher solute concentration through a semipermeable membrane Aim of this study was to formulate and evaluate oral osmotic drug delivery systems of Etoricoxib for the treatment of inflammation and arthritis. A single compartment system (tablet) and a multi-compartment system (capsule) have been prepared. The granules for the osmotic tablet were prepared by wet granulation technique using PVP K 30 in ethanol as binder. The granules were evaluated for its flow property and the tablets were compressed and coated. Then the osmotic capsules of Etoricoxib was prepared and coated. A micro orifice was drilled for the capsule. Both the tablets and capsules were evaluated and the best formulation was determined. The release studies showed that F1 formulation (osmotic tablet) which contained equal proportion of mannitol and lactose as osmogens showed a maximum release of 68.56% and was the most promising among the 6 formulations. The kinetic analysis was done for F1. The formulation was found to be stable at an accelerated temperature of 40° ± 2°C, RH 70 % ± 5 % for 45 days.

Statistical modelling of an ammonium nitrate fluidised bed granulator for inference measurement

Abstract Fluidised bed granulation is a widely used wet granulation technique. The operation of a fluidised bed granulator (FBG) as well as the quality of the product is strongly influenced by multiple process variables and disturbances. Controlling this process is difficult due to long lag times between sample analysis. Inference sensors are therefore an effective control solution for this complex process. A continuous industrial FBG was used to develop multiple linear regression (MLR) models that included two-way interaction effects. Elementary artificial neural network (ANN) models were developed to qualitatively assess the MLR models. The influences of the fluidizing air, the spray liquid and the seed particle size on the product quality were investigated and modelled. The spray liquid was found to have the largest correlation with the quality variables. Both modelling techniques produced accurate models, however undertraining of some ANN models resulted in a larger deviation between the model and validation data.

Simulation Modeling of a Pharmaceutical Tablet Manufacturing Process via Wet Granulation

The pharmaceutical tablet manufacturing process (PTMP) via wet granulation holds a critical position in pharmaceutical industry. The interest in integrating mechanistic process modeling into the pharmaceutical development has been increased because simulation model is a prerequisite for process design, analysis, control, and optimization. So the simulation modeling for PTMP via wet granulation is very necessary and significant. This study aims at proposing a simulation modeling framework for PTMP via spray fluidized bed granulation (SFBG), which is one of the most widely used wet granulation techniques in pharmaceutical industry. For SFBG, a simulation model that simultaneously involves the influences of operating variables and material attributes on average particle size (APS) is firstly developed, and then a drying model to determine the particle moisture content is introduced to be coupled with the established model predicting APS. For PTMP, considering the important effect of porosity on tablet qualities, a model describing the changes in tablet porosity is developed based on a promoted form of the Heckel equation, and then several recognized models that are all related to porosity are introduced or constructed to calculate important tablet quality indexes. The feasibility and effectiveness of the developed simulation models are validated by performing a computational experimental study to explore the scientific understanding of process and process quality control.

Enhancing dissolution of artesunate from immediate release tablets using a green granulation technique

Artesunate is a poorly soluble drug and liable to aqueous hydrolysis. This study aims to formulate Artesunate as an immediate release tablet through optimization of the melt granulation technique to improve the dissolution of the drug. Three different meltable binders were used (Polyethylene Glycol PEG 6000, Poloxamer 188 and Gelucire 50/13) for granulation step in high shear mixer prior tablets compression step applying Box-Behnken experimental design to determine the significant variables and their interactions that impact dissolution of Artesunate. Optimization mathematical models showed that by increasing binder concentration, D50 was increased, and narrow particle size distribution with minimum fines percentage was produced. Higher binder concentration and impeller speed resulted in retarding tablets dissolution. PEG 6000 and Poloxamer 188 based tablets showed faster disintegration and dissolution than Gelucire 50/13 based tablets, as well as tablets prepared by wet granulation due to hydrophilic pore forming. Melt granulation technique using a low level of PEG 6000 and Poloxamer 188 not only enhanced the dissolution of Artesunate from their immediate release tablets in comparison to traditional wet granulation technique but also maintained the stability of the product under accelerated conditions of heat and moisture.

A comprehensive analysis and optimization of continuous twin-screw granulation processes via sequential experimentation strategy

Nowadays twin-screw granulation has been emerging as an attractive continuous wet granulation technique. This study was geared towards better process design and understanding with emphasis on bridging the knowledge gap between input and output variables by employing sequential experimentation strategy. A low-dose formulation for granulation experiments contained anhydrous caffeine as the model drug. In the first phase of parameter screening, D-optimal design and stepwise regression were leveraged to develop interaction models following the examination of various quantitative and qualitative factors of potential importance. To maximize the design space dictated by predefined quality target values, several variables were fixed at optimum levels: 700 rpm screw speed, 60° kneading element staggering angle, 5 kneading elements and distributive feed screw in the screw configuration. In the second phase of characterization, response surface design was utilized to investigate the dependence of critical quality attributes of granules and tablets on selected critical process parameters (L/S ratio, throughput and barrel temperature). The results indicated that the influence of throughput and barrel temperature was relatively inferior to L/S ratio. Higher degree of liquid saturation led to granules with narrower size distribution, smaller porosity and enhanced flowability and tablets with declining tensile strength yet slackened drug release.

Formulation and evaluation of orodispersible tablets of lornoxicam

Orodispersible tablets (ODTs), also known as fast melt, quick melts, fast disintegrating have the unique property of disintegrating in the mouth in seconds without chewing and the need of water. The purpose of this investigation was to develop mouth dissolving tablets of Lornoxicam using KYRON T-314 (Polacrillin Potassium) as a novel superdisintegrant. Mouth dissolving tablets of lornoxicam were prepared by wet granulation technique using KYRON T-314 as superdisintegrant and menthol as subliming agent. The present study demonstrated potentials for rapid absorption, improved bioavailability, effective therapy and patient compliance.
 Keywords: KYRON T-314, Mouth dissolving tablet, Lornoxicam, Subliming agent, Superdisintegrant

Formulation of Herbal Fast Disintegrating Tablets and its ex-vivo Study for Anti-histaminic Activity in Guinea Pig Ileum.

The aim of present research work was to develop a herbal fast disintegrating tablet containing Fagonia schweinfurthii Hadidi dried extract and determining its antihistaminic activity using guinea pig ileum. The tablets were formulated by wet granulation technique using three different superdisintegrants (croscarmillose, crospovidone and sodium starch glycolate) at three different levels. The tablets were evaluated for various physical properties like hardness, friability weight variation etc. and various mechanical properties like disintegration time, wetting time to select the best superdisintegrant. The selected superdisintegrant was further used as intra as well as extra granulating agent to develop fast disintegrating tablets of Fagonia schweinfurthii Hadidi dried extract. The optimized formulation was subjected to stability study as per the ICH guidelines. Finally, Ex-vivo antihistaminic study was conducted on guinea pig ileum for optimized formulation and compared with marketed tablet containing cetrizine HCl as API (Stanhist-10, Ranbaxy, Pvt. Ltd). Physical properties of all tablet batches were found to be acceptable and comply with various official specifications. The disintegration time and wetting time of optimized formulation (F'3) were found to be 1.15±0.08 and 0.56±0.04 min respectively. Results of Ex-vivo study showed a comparable histamine inhibition between optimized tablet (15%) and marketed tablet formulation (18.8%) in a dose of 5 µg/ml. On the basis of in-vitro and Ex-vivo studies, it was concluded that prepared herbal fast disintegrating tablets were stable and had potent antihistaminic activity.

Transmucosal Delivery of Duloxetine Hydrochloride for Prolonged Release: Preparation, in vitro, ex vivo Characteri-zation and in vitro-ex vivo Correlation

Duloxetine hydrochloride is a selective serotonin and nor adrenaline reuptake inhibitor. It is used in the treatment of depression, diabetic peripheral neuropathic pain and in moderate to severe stress urinary incontinence in women. However, it undergoes extensive hepatic first-pass metabolism and susceptible to undergo degradation in acidic environment of stomach, which results in the poor bioavailability. The objective of the present study was to develop and evaluate the mucoadhesive buccal tablets (transmucosal delivery) of duloxetine hydrochloride with a goal of to increase the bioavailability and improve the patient compliance. Mucoadhesive buccal tablets were prepared by a wet granulation technique using mucoadhesive polymers like HPMC K4M, Carbopol 934P and PEO WSR 303. The tablets were evaluated for weight variation, thickness, hardness, friability, surface pH, swelling index, drug content uniformity, in vitro drug release, in vitro bioadhesion and ex vivo permeation studies. The physicochemical properties of all the formulations were shown to be within the limits. The optimized buccal tablets AA1, AB3 and AC1 showed prolonged drug release for a period of 6 h with the Higuchi model release profile. Further, ex vivo permeation studies for optimized tablets were conducted and shown enhanced drug permeation. Therefore, these results demonstrated that the optimized buccal formulation of duloxetine hydrochloride enhances the oral bioavailability by delivered through the buccal route.