Concentration Of Hydrophilic Polymer Research Articles

Formulation and In-Vitro evaluation of Nortriptyline Hydrochloride mucoadhesive buccal films

This contemporaneous research was aimed to formulate buccal mucoadhesive DDS to enhance bioavailability and avoid pre systemic metabolism. The mucoadhesive film was fabricated by solvent casting method with base polymer chitosan and a combination of hydrophilic polymer like PVP or Gelatin. The films were then evaluated. All the formulations were found to have optimum strength to withstand folding endurance. The films' consistent size, thickness, and weight variation were discovered. The drug content uniformity of films was exceptionally well. Given that the film's surface pH falls between 6.6 and 6.7, buccal administration is appropriate for it. The pH near to the neutral region decreases the chances of mucosal irritation. The invitro adhesion ability of the formulations were affected by the composition of chitosan and PVP or Gelatin. The lower and higher concentration of chitosan was not sufficient for invitro adhesion of films. The formulation having chitosan and hydrophilic polymers in the ratio 1:1.5 showed strong invitro adhesion. The invitro bioadhesion time of the formulations containing chitosan and gelatin or PVP was less due to poor ionization of gelatin. On increasing the concentration of hydrophilic polymers, the invitro bioadhesion time increased. The highest concentration of the polymers decreased the adhesion time. The formulation NF5 with chitosan and gelatin within the proportion of 1:1.5 exhibited drug release of 98.1% at 6 hours. The sole purpose of this work is to adhere the buccal film with the mucosa, hence formulation NF5 was selected as best formulation. Thus, current investigation's goal to develop a buccal mucoadhesive drug delivery was fulfilled.
 Keywords: Buccal film, Nortriptyline HCl, depression, in vitro studies, mucoadhesive

DEVELOPMENT AND EVALUATION OF RAMOSETRON HYDROCHLORIDE MOUTH DISSOLVING THIN FILM FOR ENHANCED THERAPEUTIC EFFICACY AND PALATABILITY

Objective: Many people have difficulties in swallowing traditional dosage forms such as tablets and capsules. The goal of this study was to develop the mouth-dissolving thin film of Ramosetron HCl (RH) for quick onset of action in the treatment of vomiting and irritable bowel syndrome, with the added benefit of disguising the bitter taste of RH. Methods: The solvent-casting approach was employed to formulate mouth dissolving thin film. The effect of variable concentrations and different grades of hydrophilic polymer HPMC (E5, E15 and E50), and plasticizers like glycerol and PEG 400 on disintegration time, drug release, thickness, tensile strength, percent elongation, folding endurance, and on appearance were studied. The optimized batch was kept for stability study at40±2 °C/75±5% RH for 30 d. Results: The formed films were transparent with a smooth surface texture. The thickness, weight variation, drug content and pH of the surface were within acceptable limits. Tensile strength and folding endurance values demonstrated adequate mechanical strength. In 45 seconds, the formulation F6 comprising HPMC E5 (150 mg) and HPMC E15 (150 mg) with PEG 400 (0.4 ml) disintegrated. The F6 formulation released 98.78±0.96 %drug in 8 min and considered as optimal formulation. The taste masking of drug was evaluated by a taste perception study using volunteers. The optimized batch was found to be stable at 40±2 °C/75±5% RH for 30 d. Conclusion: The concentration of hydrophilic polymers and plasticizers had a significant effect on the formulation and assessment characteristics of thin film. Mannitol assisted in masking the bitter taste of RH.

Formulation and Evaluation of Transdermal Patch of Thiochochicoside

The aim of the study is to formulate and evaluate transdermal patches of Thiocholchicoside In the present study, matrix type were prepared by moulding techniques. This mode of drug delivery is more beneficial for chronic disorders such as Rheumatoid arthritis which require long term drug administration to maintain therapeutic drug concentration in plasma. Transport of drugs or compounds via skin is a complex phenomenon, which allows the passage of drugs or compounds into and across the skin. In the present work an attempt has been made to formulate and evaluate the transdermal patches of Thiocholchicoside using various blends of polymer. The polymeric combinations EC/PVP and EC/HPMC used for the formulation of transdermal patches showed good film forming property. The patches formed were thin, flexible, smooth and transparent. The weight variation tests showed less variation in weight and suggesting uniform distribution of drug and polymer over the mercury surface. The thicknesses of the transdermal patches were found to increase on increasing concentration of hydrophilic polymers like PVP and HPMC.All the patches showed good flexibility and folding endurance properties. The result suggests that the formulations with increased hydrophilic polymer concentration showed long folding endurance. The moisture content in the patches was found to be low and formulations with more hydrophilic polymer concentrations showed more percentage moisture content. The in-vitro drug release studies showed that formulations TDP2, TDP3, TDP4, and TDP5 with increased concentration of hydrophilic polymer showed rapid release. The drug content analysis showed minimum variations suggesting uniform distribution of drug.

Formulation and in-vitro Evaluation of Carvedilol Gastroretentive Capsule as (Superporous Hydrogel)

The preferred route of drug administration is the oral route, but drugs with narrow absorption window in the gastrointestinal tract are still challenging. The ability to extend and monitor the gastric emptying time is a valuable tool for processes remaining in the stomach longer than other traditional dosage forms.
 The purpose of this study was to formulate and evaluate gastroretentive superporous hydrogel (SPH) of carvedilol with view to improve its solubility and increase gastric residence time in order to get sustained release formulas via utilization of various kinds and concentrations of hydrophilic polymers then after, incorporate the best prepared formula into capsules.
 Sixteenth formulae of SPH hybrid were prepared by gas blowing technique from the following materials; monomers (Poly vinyl alcohol, and Acrylamide), cross-linkers (Methylene bisacrylamide, and glutaraldehyde), hybrid agent (Chitosan), foaming agent (NaHCO3) and foam stabilizer (Tween 80). Different amounts or concentrations of these materials were utilized to investigate their effect on SPH properties (density, porosity, floating, drug content, drug release, swelling time, and swelling ratio). The soaking procedure was utilized for loading of carvedilol into SPH hybrid (6.25mg/2.5g SPH).
 After analysis the results statistically and application the similarity factor (f2) equation, formula F8 was selected as the best formula and incorporated into capsules.
 The drug release data were applied to different mathematical kinetics and the results were shown to be fitted to Higuchi model and the release mechanism was (non fickian) diffusion.
 The overall results suggested that the proposed SPH hybrid drug delivery system is encouraging for carvedilol specific delivery to the stomach.

Critical Factors for Metformin Osmotic Controlled Release Pump

Aim: Studied the critical factors in the design of an osmotic pump with metformin release rate constant at 4%/hr in diabetes mellitus within 24 hr. with the goal to reduce daily medications.
 Study Design: Experimental design 32
 Methodology: In vitro drug release profiles for 24h. The effects of different formulation variables, that is, concentration of hydrophilic polymer, diameter of drug releasing orifice and coating thickness, on the drug release profile were investigated. Also, the impact of pH, osmotic pressure and morphology with stereo microscopy and scanning electronic microscopy of the osmotic pumps were investigated. At last, osmotic pumps surface was analyze with scanning electronic microscopy.
 Results: Metformin osmotic pump were successfully prepared in this study to overcome the weak point of multiple doses and great concentration fluctuation of metformin. The formulation determined finally have a release orifice of 700 mm and 3.0% of weight gain, achieved the desired effect which can realize the constant drug release rate at the first 24 hr.
 Conclusion: The developed osmotic systems have a linear release near 4%/hr. and demonstrated that the behavior was independent of the agitation intensity and the pH of the gastrointestinal apparatus.

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.

Formulation and Evaluation of Silymarin Microcrystals by In- Situ Micronization Technique

Silymarin (SM) is a plant extract obtained from Silybum marianum( milk thistle) . It is class II type drug according to Biopharmaceutics Classification System with low bioavailability due to its low solubility.
 Micro/nanonization during crystallization, surface modification and crystal structure modification may improve the dissolution rate of poorly water-soluble drugs.
 The aim of this study was to increase the water solubility and dissolution rate of SM by in-situ micronization using solvent change either by stirring or ultrasonic method. Stabilizers like Gelatin, PVP-K30, HPMC15, Pulullan were used to stabilize the prepared ultrafine crystals. Effect of type and concentration of hydrophilic polymer, solvent: antisolvent volume ratio and the effect of ultrasonic irradiation were studied. The prepared microcrystals were evaluated for their %yield, water solubility, crystals structure by XRD,DSC, and SEM. Particle size and dissolution rate were also tested . Silymarin microcrystals prepared by ultrasonic method and stabilized by 0.1%gelatin using 1:2 solvent: anti-solvent volume ratio showed the best results with particle size reduction from mean diameter of 1.5µm (untrated silymarin) to 0.43µm with uniform morphology and enhanced solubility and dissolution.

DESIGN AND IN VITRO CHARACTERIZATION OF FLOATING TABLETS OF METRONIDAZOLE

Objective: The objective of the present study was to formulate the effervescent floating matrix tablet of metronidazole and to evaluate the effect of varying concentrations of hydrophilic polymers on drug release.
 Methods: Drug excipients interaction was studied by Fourier transform infrared spectrophotometer. The effervescent floating matrix tablets were prepared by direct compression technique using hydroxypropyl methylcellulose (HPMCK4) and xanthan gum alone and in combination as release retardants. Microcrystalline cellulose was used as diluent. Sodium bicarbonate was used as effervescent agent. The prepared matrix tablets were evaluated for their physicochemical parameters such as weight variation, hardness, friability, content uniformity, buoyancy time, and in vitro dissolution.
 Results: Micromeritic properties and post-compression parameters were evaluated and all the parameters were found within the acceptable limit. The drug release data were subjected to different models to evaluate release kinetics and mechanism of drug release. The matrix tablets prepared with xanthan gum and a mixture of xanthan gum and HPMCK4 were retarded the drug release up to 12 h. The release mechanism of metronidazole was evaluated on the basis of release exponent n value in Peppas model. The n value of the formulations ranged from 0.46 to 0.89 which indicated Case II transport and zero-order release.
 Conclusion: Floating matrix tablet is the simple, efficient, and economic method to sustain the release of metronidazole to eradicate Helicobacter pylori in peptic ulcer disease.

Effect of hydrophilic and hydrophobic polymers on permeation of S-amlodipine besylate through intercalated polymeric transdermal matrix: 3(2) designing, optimization and characterization

Objective: Innovation in material science has made it possible to fabricate a pharmaceutical material of modifiable characteristics and utility, in delivering therapeutics at a sustained/controlled rate. The objective of this study is to design and optimize the controlled release transdermal films of S-Amlodipine besylate by intercalating hydrophilic and hydrophobic polymers.Methods: 3(2) factorial design and response surface methodology was utilized to prepare formulations by intercalating the varied concentration of polymers(A) and penetration enhancer(B) in solvent. The effect of these independent factors on drug release and flux was investigated to substantiate the ex-vivo, stability and histological findings of the study.Results: FTIR, DSC revealed the compatibility of drug with polymers; however, the semicrystallinity in drug was observed under PXRD. SEM micrographs showed homogeneous dispersion and entanglement of drug throughout the matrix. Results from the permeation study suggested the significant effect of factors on the ex vivo permeation of drug. It was observed that drug release was found to be increased with an increase in hydrophilic polymer concentration and PE. The formulations having polymers (EC:PVPK-30) at 7:3 showed maximum drug release with highest flux (102.60 ± 1.12 µg/cm2/h) and permeability coefficient (32.78 ± 1.38 cm/h). Significant effect of PE on lipid and protein framework of the skin was also observed which is responsible for increased permeation. The optimized formulation was found to be stable and showed no-sign of localized reactions, indicating safety and compatibility with the skin.Conclusion: Thus, results indicated that the prepared intercalated transdermal matrix can be a promising nonoral carrier to deliver effective amounts of drug.

EFFECT OF POLYMERS ON THE PHYSICOCHEMICAL AND DRUG RELEASE PROPERTIES OF TRANSDERMAL PATCHES OF ATENOLOL

Objective: The objective of this research work was to develop a transdermal drug delivery system containing atenolol with different ratios of hydrophilic and hydrophobic polymeric combinations, using solvent evaporation technique and to examine the effect of hydrophilicity and hydrophobicity of polymers on the physicochemical and drug release properties of transdermal patches.Methods: Solvent casting method has been used to formulate transdermal patches. Hydroxypropyl methylcellulose (HPMC), Polyvinylpyrrolidone (PVP), Ethylcellulose (EC) in different combination ratios were used as the polymer. Propylene glycol was used as a plasticizer. Permeation enhancers such as span 80 were used to enhance permeation through the skin. In vitro diffusion study was carried out by franz diffusion cell using egg membrane as a semi-permeable membrane for diffusion.Results: Result showed that the thickness of the all batch of patches varied from 0.32 to 0.39 mm with uniformity of thickness in each formulation. Formulations F1 to F3 had high moisture content varied from 2.07±0.09 to 2.56±0.15 and high moisture uptake value varied from 3.21±0.35 to 4.09±0.38, due to a higher concentration of hydrophilic polymers. Drug content of all batches was ranged between 85.92±1.32 to 95.71±1.42. Folding endurance values off all batches were more than 75. Formulation batches F1 to F3 showed higher cumulative drug release varied from 61.34% to 68.11% as compared to formulation batches F4 to F6.Conclusion: Higher proportion of hydrophilic polymer in the formulation of transdermal patches, gives higher percentage drug release from prepared patches. The finding of the study indicates that hydrophilicity and hydrophobicity of polymer effects the physicochemical and drug release properties of transdermal patches and an optimum proportion of hydrophilic and hydrophobic polymer is required for the preparation of effective transdermal patches.

Effect of hydrophilic and hydrophobic polymer on the release of ketoprofen and allopurinol from bilayer matrix transdermal patch

AbstractThe aim of this study was to design a matrix transdermal patch of ketoprofen and allopurinol for the possible treatment of arthritis with reduced side effects. For this purpose, a bilayer matrix transdermal patch was prepared with an immediate release layer of Methocel containing ketoprofen while secondary sustained layer composed of allopurinol with combinations of Eudragit RL100 and Methocel. The patch was studied for swelling index in distilled water and was found to increase with an increase in concentration of hydrophilic polymer. The in vitro dissolution was conducted in USP dissolution apparatus II using phosphate buffer saline (pH 7.4) as dissolution medium at 37 ± 2°C. Based on in vitro dissolution studies, KA1BL (99.65% release in 10 hr) was selected for ex vivo permeation studies through Franz diffusion cell using excised abdominal skin of albino rats, and using clove oil and menthol as permeation enhancers. The optimized formulation KA1BL‐M3 released 69.37% drug over 12 hr and followed zero‐order kinetics with anomalous release mechanism. The patch had uniform distribution of components as per digital microscopic analysis.

DESIGN, FORMULATION AND IN VITRO DRUG RELEASE FROM TRANSDERMAL PATCHES CONTAINING IMIPRAMINE HYDROCHLORIDE AS MODEL DRUG

Objective: The aim of the present investigation was to form matrix type transdermal patches containing imipramine hydrochloride were prepared using two polymers by solvent evaporation technique to minimise the dose of the drug for lesser side effect and increase the bioavailability of a drug.Methods: In the present study, drug loaded matrix type transdermal films of imipramine hydrochloride were prepared by the solvent evaporation method with the help of polymers along with polyethene glycol (PEG) 400 was used as plasticizer and dimethyl sulfoxide (DMSO) was used as penetration enhancer. Drug-polymer interactions determine by FTIR and a standard calibration curve of imipramine hydrochloride was determined by using UV estimation.Results: The formulated transdermal patch by using PVP K-30, HPMC K100M showed good physical properties. All prepared formulations indicated good physical stability. The formulation F-1 gave the most suitable transdermal film with all desirable physicochemical properties. The thickness of the patches was varied from 0.263±0.67 mm to 0.301±0.61 mm, uniformity of patches showed that patches prepared by solvent evaporation while low standard deviation values ensued by thickness measurements of the film, and weights ranged between 50.5±0.75 mg and 52.15±2.15 mg, which indicates that different batches patch weights, were comparatively similar. Folding endurance was found to be>200 that is satisfactory for the patches, drug content was found to be 5.33±0.14 mg to 5.57±0.095 mg. In vitro, drug permeation studies of formulations were performed by using K-C diffusion cells using abdomen skin of the albino rat. The results were best in in-vitro skin permeation through rat skin as compared to all other formulations prepared with a hydrophilic polymer containing permeation enhancer. The formulation, F1 is considered as the best formulation, since it shows maximum in vitro drug release as 84.71±3.07 % at 24 h. The drug release kinetics studies showed that the majority of formulations were governed by Higuchi model and mechanism of release was non-Fickian mediated.Conclusion: In conclusion, controlled release transdermal drug delivery system (TDDS) patches of imipramine hydrochloride can be prepared using the polymer combinations, with plasticizer and enhancer. The release rate of drug through patched increased simultaneously as the concentration of hydrophilic polymer was increased. However, the mechanism of drug release of all formulations was non-Fickian. The properties of a film did not change during the period of study.

Solubility of cilostazol in the presence of polyethylene glycol 4000, polyethylene glycol 6000, polyvinylpyrrolidone K30, and poly(1-vinylpyrrolidone-co-vinyl acetate) at different temperatures

The solubilities of cilostazol in aqueous solutions containing polyethylene glycol 4000 (PEG 4000), polyethylene glycol 6000 (PEG 6000), polyvinylpyrrolidone K30 (PVP K30), and poly(1-vinylpyrrolidone-co-vinyl acetate) (PVP/VA) are measured at temperatures ranging from 298.15 to 318.15K. It increased with the increase in the hydrophilic carrier concentration and temperature. PVP/VA was the most effective polymer to solubilize cilostazol. The transfer Gibbs free energy (ΔtrG°) and enthalpy (ΔtrH°) values were negative, indicating that the transfer of cilostazol from only water to an aqueous hydrophilic polymer solution is spontaneous and energetically favorable. Furthermore, the ΔtrG° and ΔtrH° values decreased with the increase in the hydrophilic polymer concentration, indicating that solubilization is more favorable with the increase in the hydrophilic polymer concentrations. In particular, the ΔtrG° values considerably decreased for PVP/VA compared to PEG 4000, PEG 6000, and PVP K30. This result indicated that PVP/VA is an effective solubilizing additive for developing oral solid formulations of cilostazol.

Formulation and evaluation of tamarind seed polysaccharide matrix tablet

Objective: The objective of using natural polymer was to modify the release rate of Diclofenac sodium from matrix tablet. The matrix forming agent like Tamarind seed Polysaccharide show sustained release property in tablet which is obtained naturally from fruit of Tamarindus indica L. belonging to Family Leguminosae. Methods: The sustained release matrix tablet of Diclofenac sodium were prepared by wet granulation technique using varying concentration of hydrophilic polymer i.e. TSP. Results: OF1 and OF2 both are optimized batch. The in vitro dissolution study was carried out for optimized as well as marketed formulation (Voveran- SR). Both the optimized batchesat 10 h were found to be 90.27% and 90.18%, respectively. Conclusions: Tamarind seed polysaccharide can be employed in dosage form to sustain the drug release. Tablet formulated with various concentrations of Tamarind seed polysaccharide (TSP) gives release up to 10 h and more. OF1 and OF2 both formulations give comparable release with marketed formulation. From the present work it can be conclude that, the objectives which were set at the beginning of the study got fulfilled.

Effect of HPMC concentration on β-cyclodextrin solubilization of norfloxacin

The effect of hydroxypropyl methylcellulose (HPMC) concentration on β-cyclodextrin (β-CD) solubilization of norfloxacin was examined. The solubility and dissolution of norfloxacin/β-CD and norfloxacin/β-CD/HPMC inclusion complexes were studied. The presence of β-CD increased significantly the solubility and dissolution of norfloxacin. The addition of HPMC until 5% (w/w) improved the solubilization of norfloxacin but further addition above 5% (w/w), decreased norfloxacin solubilization. Fourier transformed Infra-red (FTIR) showed that norfloxacin was successfully included into β-CD. Differential scanning calorimetry (DSC) showed that the norfloxacin endothermic peak shifted to a lower temperature with reduced intensity indicating the formation of inclusion complex. The addition of HPMC reduced further the intensity of norfloxacin endothermic peak. Most of the sharp and intense peaks of norfloxacin disappeared with the addition of HPMC. In conclusion, the concentration of hydrophilic polymer used to enhance β-CD solubilization of poorly soluble drugs is very critical.

FORMULATION AND IN-VITRO EVALUATION OF SUSTAINED RELEASE MATRIX TABLETS OF GLIPIZIDE

Diabetes mellitus is a metabolic disorder caused by insufficient production of endogenous insulin, with or without resistance to insulin action, resulting in hyperglycaemia. In type 1 diabetes mellitus, there is a failure in production of insulin as a result of destruction of the cells of the pancreas, and patients require treatment with insulin whereas type 2 diabetes can be characterised by defects in both insulin action (i.e. insulin resistance) and insulin secretion, and is associated with elevated basal hepatic glucose production. Glipizide is a second-generation sulfonylurea that can acutely lower the blood glucose level in humans by stimulating the release of insulin from the pancreas and is typically prescribed to treat type II diabetes. Different formulations were prepared by varying the concentration of HPMC used as polymers. The effect of varying concentration of hydrophilic polymers (HPMC 5cps and 15 cps) was studied on the release pattern of glipizide. Sustained release glipizide matrix tablets were prepared by wet granulation and compression of hydroxypropylmethyl cellulose (5 cps and 15 cps), drug and other excipients mixture. The promising formulation was compared with the marketed sample of suatained release glynase in terms of release pattern. The release rate of a glipizide from matrix tablet was decreased with increasing the concentration as well as viscosity polymer. This might be probably due to increased swelling and reduced erosion rate of matrix tablet. The formulation 13 (F13) showed the similar result as marketed sample of sustained release glynase tablets in terms of release rate. Key Words: Glipizide, Hydroxy propyl methyl cellulose (HPMC), Viscosity grades

Losartan potassium loaded sustained release matrix tablets: Influence of various hydrophilic and hydrophobic polymers on drug release behaviour

Losartan potassium is an angiotensin II receptor antagonist readily absorbed from the GIT, following oral administration. It has low bioavailability as it undergoes extensive first pass metabolism and low elimination half-life. The present study was aimed at studying sustained release behaviour of the drug using hydrophilic and hydrophobic polymers and to optimise using a 32 full factorial design. Eudragit and HPMC were used to evaluate the effect of hydrophilic and hydrophobic polymers on the release pattern of the drug. A full factorial was implemented at 20, 30 and 40% concentration of hydrophilic polymer and 2.5, 5 and 7.5% of hydrophobic polymer correlating with the release behaviour. Process variables were investigated and the results showed excellent adaptability in releasing drug over prolonged periods. Based on the results, it was found suitable to formulate a dosage form using optimum concentration of hydrophobic polymer along with hydrophilic polymer to vary the release behaviour for over 12 hours.

Inlay osmotic pump tablets containing metformin and glipizide

The goal of diabetes therapy today is to achieve and maintain as near normal glycemia as possible to prevent the long-term microvascular and macrovascular complications of an elevated blood glucose. A newly developed inlay osmotic pump tablet (IOPT) can deliver glipizide (GLZ) and metformin HCl (MET) gradually in controlled manner. The aim of present investigation was to prepare the IOPT that can deliver >75% of GLZ in 2 h, whereas MET released after 2 h and sustained up to 12 h. In the present work, HP-β-CD was used to modify the solubility of GLZ before incorporating in the osmotic system and MET was spray-dried with HPMC A15C to modify its release profile, flow property, and compressibility. Various parameters mainly G75% (75% GLZ release), tLMET (lag time of MET release from device), Q10 h (percent of MET released within 10 h), and RSQZERO (R2 of release data fitted to zero-order equation) were used to compare different formulations. The effects of different formulation variables, that is, osmagents, concentration of hydrophilic polymer, diameter of drug releasing orifice, and coating composition on the drug release profile were investigated. The release rate of GLZ could be effectively modified by the addition of sodium carbonate and sodium chloride, whereas the release rate of MET was adjusted by dual-coating system and by addition of hydrophilic polymer. The developed inlay osmotic system could be effective in the multidrug therapy of diabetes by delivering both drugs in a controlled manner.

Indomethacin sustained release pellets prepared by extrusion-spheronization

Gastrointestinal side effects may interrupt essential therapy with indomethacin, a non-steroidal anti-inflammatory drug. Formulation of this drug into sustained release multiparticulate form may reduce some of these side effects by avoiding contact of drug crystals with gastrointestinal mucosa at high concentrations, as may happen with immediate release dosage forms. Indomethacin (IM) sustained release pellets containing 5 or 10 % w/w of the drug were prepared using an extrusion-spheronization technique. Different concentrations of hydrophilic polymers, polyethylene glycol 4000 (PEG 4000), hydroxypropyl methylcellulose E5 LV premium (HPMC) and polyvinyl pyrrolidone (PVP K30), were mixed at different concentrations (5,10 and 20 %) with Avicel PH 101 to prepare the sustained release formulae. Moreover, a mixer torque rheometer was used to quantitatively determine the suitable moisture content in the pastes before the extrusion process. The resulting pellets were characterized for content, particle size, shape and dissolution profile. The studies on the effect of the polymers used on Avicel rheological properties revealed that the magnitude of torque for the system was decreasing as the polymer concentration increased. The in vitro release of IM from the prepared Avicel pellets was found to be dependent upon the type and concentration of the added polymer. The rank order of IM release in the presence of the investigated polymers was as follows: PEG > HPMC > PVP. Furthermore, the magnitude of IM release rate from the pellet formulations was found to be dependent on the magnitude of the peak torque of the pellet forming paste, which in turn depends on the type and concentration of the added polymer. Increasing IM loading from 5 to 10 % has led to an increase in dissolution rates. At least two of the prepared pellet formulations showed dissolution profiles similar to the commercial product Bonidon 75 SR capsules. In conclusion, the formulation of IM sustained release pellets successfully controlled the drug release which might be beneficial in lowering the risk of side effects and improving patient convenience as an advantage of the pellets as a drug delivery system.

Influence of polyethylene glycol/polyethylene oxide on the release characteristics of sustained-release ethylcellulose mini-matrices produced by hot-melt extrusion: in vitro and in vivo evaluations

Mini-matrices with release-sustaining properties were developed by hot-melt extrusion (diameter 3 mm, height 2 mm) using metoprolol tartrate as model drug (30%, w/w) and ethylcellulose as sustained-release agent. Polyethylene glycol or polyethylene oxide was added to the formulation to increase drug release. Changing the hydrophilic polymer concentration (0%, 1%, 2.5%, 5%, 10%, 20% and 70%, w/w) and molecular weight (6000, 100,000, 1,000,000 and 7,000,000) modified the in vitro drug release: increasing concentrations yielded faster drug release (irrespective of molecular weight), whereas the influence of molecular weight depended on concentration. Smooth extrudates were obtained when processed at 40 and 70 °C for polyethylene glycol and polyethylene oxide formulations, respectively. Raman analysis revealed that metoprolol tartrate was homogeneously distributed in the mini-matrices, independent of hydrophilic polymer concentration and molecular weight. Also drug and polymer crystallinity were independent of both parameters. An oral dose of 200 mg metoprolol tartrate was administered to dogs in a randomized order either as immediate-release preparation (Lopresor ® 100), as sustained-release formulation (Slow-Lopresor ® 200 Divitabs ®), or as experimental mini-matrices (varying in hydrophilic polymer concentration). The sustained-release effect of the experimental formulations was limited, and relative bioavailabilities of 66.2% and 148.2% were obtained for 5% and 20% PEO 1,000,000 mini-matrices, respectively.