Controlled Release Matrix Tablets

The objective of this work was to develop and characterize controlled release matrix tablets of Pioglitazone an antidiabetic drug using gum derived from oats (Avena sativa) as a release retardant agent. This gum extracted from oats by an established method. Fourier transform infrared spectroscopy studies were performed to find out the interactions between gum and drug. There was no significant interaction between drug and gum. Here matrix tablets of Pioglitazone were prepared with different ratios of gum alone and in combination with PVP by direct compression technique. Tablets thus formulated were evaluated for various quality control tests like weight variation, hardness, friability etc. All matrix tablets were found to have better uniformity of weight and drug content. After evaluation of physical characteristics of tablets, the in vitro dissolution test was performed in 0.1 N HCl up to 24 hours. The formulations PAMP3, PAMP4 and PAMP5 containing both gum and PVP controlled the release of drug up to 24 hours. The kinetic release data fitted into different mathematical models (Zero order, First order, Higuchi, Peppa’s and Hixson-Crowell). Most of the solid matrix formulations followed Higuchi or zero order kinetics.

In this study matrix tablet of labetalol hcl were prepared by wet granulation technique, using HPMC K- 4M, and HPMC k-15 and cardopol polymers as retardant. The drug-polymer ratio was found to influence the release of drug from the formulations. It was found that increase in the concentration of HPMC K-4M in polymeric ratio decreases the drug release. HPMC K-4M is non carcinogenic, biocompatible and has high drug holding capacity at the same time it is effective in retarding the drug release. The formulations F-3, showed good drug release with good matrix integrity. Different parameters like hardness, friability, weight variation, drug content uniformity, in-vitro drug release were evaluated. Based on these results formulation F-3was found to be the most promising formulations. The results suggest that the developed controlled-release matrix tablets of labetalol hcl could perform better than conventional dosage forms, leading to improve efficacy and better patient compliance. Thus the aim of this study was achieved. Further preclinical and clinical studies are required to evaluate the efficacy of these formulations of labetalol hcl in the management of Hypertension.

The study was aimed for developing controlled release matrix tablets of highly water-soluble Metformin hydrochloride by wet granulation method using Lannea coromandelica plant gum, hydroxypropylmethylcellulose (HPMC) and xanthane gum as polymers. The flow properties of blended powders, crushing strength, friability, swelling index and drug content uniformity of compressed tablets were determined. In vitro drug release studies of the matrix tablets were conducted in simulated gastric fluid (pH 1.2), simulated intestinal fluid (pH 6.8) and the kinetics of drug release was determined by fitting the release data to different kinetic models. Lannea coromandelica plant gum was found to be best suitable for wet granulation method, having a good compressibility index value of less than 20. The metformin hydrochloride matrix tablets produced generally possessed fairly good physical properties. Tablet swelling and drug release in aqueous medium were dependent on the type and amount of release retarding polymer and the solubility of drug used. Controlled release of metformin from the matrix tablets in aqueous medium was achieved by selected polymers. Drug release from metformin hydrochloride tablets fitted to zero order, first order and Higuchi model. The drug release mechanisms from the matrix tablets were found to be linear with all the matrix tablets with correlation coefficient (r 2 ) values > 0.956.

The selected gum was used for the preparation of the controlled release matrix tablets of the model drug, losartan potassium using drug- polymer ratios of 1:0.25, 1:0.5 and 1:0.75. (Table 1) 300 tablets were prepared in each batch by direct compression method because of the good flow properties of the powder blend as per the initial studies carried out. Required quantities of powder was weighed and mixed in a geometric dilution pattern. The final powder blends ready for compression were further evaluated to conform the flow properties by using compressibility index, Hausener‟s ratio and angle of repose. The powder blends were compressed in to tablets by using an Elite 10 station minipress with 8 mm diameter flat round punches with a compression force sufficient to obtain hardness in the range of 4-6 kg/cm 2 .

Oral controlled release matrix tablets each containing 90mg of Diltiazem hydrochloride were prepared by wet granulation method using different drug: gum ratios viz. 1:0.25, 1:0.5, 1:1 and 1:1.25 for various formulations containing Aegle marmelos gum. The composition of different formulations of Diltiazem Controlled Release tablets is shown in Table 2. All the ingredients of the formulation were accurately weighed and the coherent mass was formed using distilled water as granulating fluid. The coherent mass was passed through mesh No. 12 and the granules obtained were air dried. The lubricants talc (2%) and magnesium stearate (2%) were passed through mesh No. 60 onto the dry granules and blended in a closed polyethylene bag. The tablet granules were compressed into tablets on an 8 – station tablet punching machine (Shakthi Pharmatech Pvt Ltd., Ahmedabad) to a hardness of 5 – 6 kg/sqcm. The compressed tablets were stored in a closed container.

The present work was aimed to evaluate SAGO starch in controlled release matrix tablets of Tramadol HCL to optimize the release of the drug for 12 hrs to act as twice daily formulations. Controlled release polymer, HPMC (K4M) was used in the ratio of 3:1 to the drug. High concentration of the polymer is intentionally used keeping the swelling power and gel forming ability HPMC. Matrix tablets, TS-1 to TS-6 were prepared using wet granulation technique with 5% corn starch as granulating agent and 0, 5%, 10%, 15%, 20% and 25% of SAGO starch to the drug. The prepared tablets were evaluated for tabletting characteristics like weight variation, hardness, friability and drug content uniformity, and found that they were within the compendial limits. It is found that the SAGO starch enhanced the drug release from prepared controlled release formulations proportional to the concentration used in tablets. TS-4 was found to be the optimized formulation which has a release of more than 94.58% in 12 hrs having 15% SAGO. The release kinetics of the optimized formulation indicates that it has zero order release with erosion mechanism.

The aim of the present work was to design controlled release matrix tablets of Cephalexin by incorporating the drug in a matrix made up of using combination of low concentration of hydrophobic polymer and hydrophobic polymers, to study their release pattern and release mechanism of the drug from matrix tablets upto 12 hours. Hydrophobic polymer is the rate retardant material, but different combinations with hydrophilic polymer increase the release rate to establish intended drug release up to 12 hours. Matrix tablets were formulated with the combination of hydrophobic to hydrophilic polymers in the ratios of 1:1, 1:2, 1:3 and 1:4. F1 to F4 formulation were prepared with ethylcellulose (EC) and hydroxypropyl methyl cellulose (HPMC K4M), F5 to F8 were prepared with EC and HPMC K15M and F9 to F12 were prepared with EC and HPMC K100M. Designed matrix tablets were evaluated for various pre-compression and post-compression parameters. F4 is the optimized formulation, showed 100.34% release at the end of 12 hours as it showed good release rate profile compared to all formulations. Drug released pattern followed zero order with non-Fickian diffusion method.

In the present research, an attempt has been made to formulate controlled release matrix tablets of nicotinic acid (NA), using xyloglucon (XGL), xanthan gum and guar gum separately, which tend to reduce “flushing” effect caused by immediate release of NA. Tablets were evaluated for uniformity of weight, content of active ingredient, friability, hardness, thickness, in vitro dissolution and swelling index. All the formulations showed compliance with pharmacopoeial standards. After hydration of gum, drug release was essentially pH-independent. The amount released was directly proportional to the loading of dose and inversely proportional to gum concentration in tablets. Selected formulations were subject to stability studies, which showed stability with respect to release pattern. It can be concluded that, apart from guar gum, and xanthan gum the XGL can be successfully used as an effective matrix material to retard the release of NA for extended period of time.

Matrix tablets were prepared by direct compression method. The composition of various formulations was shown in Table 1. Trimtazidine Di Hydrochloride, Polysaccharide B-1459 Colloidal anhydrous silica, Polyethylene oxide and anhydrous calcium hydrogen phosphate through #30 mesh and Magnesium stearate through #40 mesh and collect separately in polyethylene bag. Tablets were compressed at 210 mg weight on a 16-station rotary tablet punching machine (Cadmach Machinery pvt. Ltd,) with 8mm circular shaped deep concave punches plain on both sides [7] After compression, the matrix tablets were film coated with a non-cellulosic polymer, namely Opadry II Pink, containing PVA, for good appearance and to protect the tablet from environment. [8] Six different formulae, having different concentrations were developed to evaluate the drug release and to study the effect of polymer concentration on drug release.

14. Rajesh. N, Siddaramaiah and D.V. Gowda., et al. 57 studied on the controlled release behavior of diltiazem hydrochloride from the Pellets of chitosan and microcrystalline cellulose to minimize the unwanted toxic effects of Diltiazem Hydrochloride by kinetic control of drug release. 12 ml of deminerlized water was used as binding agent volume of binding agent increases, irregularly shaped pellets were produced. As the volume of the binding agent was less than 12 ml, requires more pressure for compaction and difficult to separate as an individual pellets. The percent of wetting solution and volume of binding agent has also an effect on the sphericity of the pellets, confirmed by SEM photographs. Result showed that lowered drug release was noticed for the systems containing higher content of MCC. Because swollen MCC particles retards the penetration of dissolution media into pellets and thus limiting the release of drug from pellets.

Theophylline is a bronchodilator that relieves airflow obstruction in chronic asthma and decreases its symptoms. Theophylline is well absorbed by the gastrointestinal tract, and several sustained-release preparations are available. Previously the mainstay of asthma therapy, theophylline has been largely replaced with β 2 agonists and corticosteroids due to a narrow therapeutic window, high side-effect profile, and potential for drug interactions. Overdose may cause seizures or potentially fatal arrhythmias. Theophylline is metabolized in the liver, is a CYP1A2 and 3A4 substrate, and interacts adversely with many drugs [1] .

Since CPT is poorly water soluble drug, its release from CR matrix tablet is incomplete and therapeutically effec- tive drug levels may not be achieved. Hence, in the pres- ent investigation cyclodextrins like β-CD and HP-β-CD at a level of 20% w/w of total tablet weight (F5 and F6) were included in the formulations and their effect on the CPT release was studied in order to achieve thera- peutically effective levels of CPT. A 96.23 ± 1.27% CPT release was observed at end of 12 h with F5 con- taining β-CD (20% w/w) and 98.4 ± 1.02% of CPT release was observed at end of 12 h with F6 containing HP-β-CD (20% w/w). The initial release of CPT at 1 h was 10.17 ± 0.39, 15.98 ± 0.42 and 22.27 ± 0.92 respec- tively for F4, F5 and F6. The addition of cyclodextrins significantly increased the initial burst release of CPT from the formulations. The CPT release was more with HP-β-CD when compared to β-CD. This is because of more hydrophilic nature of HP-β-CD than the β-CD.

Oral ingestion is traditionally preferred route of drug administration, providing a convenient method of effectively achieving both local and systemic effects. In conventional oral drug delivery systems, there is very little control over release of drug. The effective concentration at the target site can be achieved by intermittent administration of grossly excessive doses, which in most situations, often results in constantly changing, unpredictable and often sub or supra therapeutic plasma concentrations leaving the marked side effects.

Controlled release tablet will provide a long lasting and more reliable release of drug in GIT to develop a once daily formulation. They prolong the dosing intervals and increases patient compliance than the existing conventional dosage forms. 1 Theophylline is an oral bronchodilator medicine which is prescribed for people with breathing problems, such as asthma and chronic obstructive pulmonary disease (COPD). It is a BCS class I drug with high solubility and high permeability. The lowest levels of epinephrine and cortisol in the body around 10 PM to 4 AM and elevated histamine and other mediator levels that occur between midnight and 4 AM, play a major role in the worsening of asthma during the night. 2 By formulating a controlled release Theophylline matrix tablets we can control the release up to 12 hours, so that we can effectively control the asthma throughout the sleep. The objective of the present study is to prepare controlled release tablets of Theophylline with natural gums i.e., guar gum and xanthan gum, to evaluate pre and post compression parameters and to determine drug-excipient compatibility. Natural gums are used as they are safe, easily available and cost effective. By using combination of guar gum and xanthan gum controlled release was obtained with 1:0.5 drug and polymer ratio. The optimized formula was F 7. The Hardness of the tablets ranged between 4.0 Kg/Cm 2 to 6.5 Kg/Cm 2 . The

The results of the weight variation, hardness, thickness, friability, and drug content of the tablets are given in table 5. All the tablets of different batches complied with the official requirements of weight variation as their weight variation passes the limits. The hardness of the tablets ranged from 2.8 to 3.3kg/cm 2 and the friability values were less than 0.6% indicating that the matrix tablets were compact and hard. The thickness of the tablets ranged from 1.48 to 1.86 mm. All the formulations satisfied the content of the drug as they contained 90 to 100% of simvastatin and good uniformity in drug content was observed. Thus all the quality control parameters of the prepared tablets were found to be practically within limits.

Conventional dosage forms are the most preferred and convenient option for drug delivery. However, it has poor patient compliance with ensuing undesirable toxicity and poor efficiency. A major challenge thus lies in optimizing the properties of the drug and its delivery mechanism in producing safe and efficient drugs. Consequently, there is a need for new drug delivery systems and they represent one of the frontier research areas [1,2]. An appropriately designed controlled drug delivery system can be a major advance concerning the targeting of drug to a specific organ or tissue and controlling the rate of drug delivery to the target site. A controlled release formulation that maintains an adequate and desired release of the drug over an extended period of time offers optimum biological response, prolonged efficacy, decreased toxicity and reduction in the drug plasma level fluctuation compared to conventional modes of delivery. Controlled drug delivery system dispenses the drug locally or systemically at a predestined rate for a specified period. Matrix tablets offer an effective means of oral controlled release formulation. They maintained therapeutic concentrations over prolonged periods and manufactured at a low cost. Various types of polymers have been used as release rate modifiers to formulate matrix tablets. Over the years, Gums and Mucilage’s are more oftenly used for the preparation of normal conventional dosage forms and also novel drug delivery systems. The use of polymers and other materials to prolong the drug release rate has become more popular. Natural polymers are better than the synthetic polymers because they are inert, non-toxic, low costand are also degradable in the body itself [3,4]. Natural polymers produce an appropriate drug release profile and are cost-effective. They have high gelling capacity and the drug releases when the polymer swells on contact with the aqueous medium. Drug releases through diffusion, dissolution and erosion mechanism [5]. Torsemide is a new generation loops diuretic belonging to pyridine sulfonylurea class and has been used for the treatment of both acute and chronic congestive heart failure, liver cirrhosis, and arterial

The control release tablets of Finasteride were prepared with individual and different combinations of polymers with different ratios.F1, F2, F3 are prepared, drug with HPMC E-5M with ratios of 1:1, 1:2, 1:3. F4, F5, F6 are prepared with HPMC K-100M with ratios of 1:1,1:2,1:3. F7, F8, F9 are prepared with Eudragit with ratios of 1:1, 1:2,1:3. F10 is the combination of HPMC E-5M and HPMC K-100M with the ratios of 1:1, F11 is the combination of HPMC E5m and Eudragit with the ratios of 1:1. F12 is combination of three polymers with 1:1:1 ratio. Formulations are prepared with respectively of F1, F2 &F3 failed. Because the drug was not released in controlled manner. In f4, F5, F6 lag time is not maintained and also total amount of the drug is not released until 24 hours. F10, F11, F12 are giving good results but half-life is less comparing with Eudragit polymer. Hence F10- F12 formulations are also failed. In F7 & F8 maximum amount of drug is released in 24 hours but the lag time is not maintained properly. By increasing the ratio of polymer in F9 lag time is maintained and the control release of the drug occurs, which indicates that F9 is the optimized formulation.

The aim of the current study was to design oral controlled release matrix tablets of losartan potassium. Tablets were prepared by direct compression and evaluated for hardness, friability, thickness, drug content and in vitro dissolution parameters. Carbopol 934P and HPMC K 100M (hydroxyl propyl methyl cellulose) were used as the polymers . In vitro release studies were conducted in phosphate buffer pH 6.8 for 24 hours. All the formulations showed controlled release of losartan potassium over a period of 24 hours. The release profile of losartan potassium from all the formulations (except F2, F3, F8 which showed first order release) are close to zero order and follow diffusion dependent release. Irrespective of the polymer type and its concentration, the prepared hydrophilic matrix tablets showed non-fickian (anomalous) release, coupled diffusion and polymer matrix relaxation as the values of release exponent (n) are in between 0.584 and 0.8692. Finally it was clear that HPMC K100M and Carbopol 934P are good candidates for preparing controlled release matrix tablets of losartan potassium.

The aim of this work was preparation and evaluation of diclofenac sodium controlled release matrix tablets using various proportions of natural polymer Abelmoschus esculentus mucilage powder (i.e;Drug:Polymer ratio-1:0.25,1:0.5,1:1,1:1.5,1:2) as release controlling factor by Wet Granulation method. The tablets were evaluated for various parameters like friability, weight variation, hardness, drug time, content uniformity. In vitro drug release characteristics of dosage form was evaluated in 6.8 pH phosphate buffer. All the formulations followed zero order kinetics along with diffusion mechanisms. From In vitro release data, formulation F4 containing Drug:Polymer (1:1.5) showed maximum drug release of 99.8% . All the formulations F1 to F5 undergo Non-Fickian diffusion or Enomalous diffusion mechanism. Analysis of drug release rate from matrix system indicated drug was release by super case-II transport mechanism.

The study was obtained to develop oral controlled release matrix tablets of Lamivudine having different proportion of Guar gum (retardant polymer) and to study the effect of formulation factor such as polymer proportion on the in- vitro release. The prepared granules were evaluated such as angle of repose, loose bulk density, tapped bulk density and compressibility index and satisfactory results were obtained. Compressed tablets were also evaluated for uniformity of weight, content of active ingredient, thickness, friability, hardness, swelling, erosion behaviour and in-vitro dissolution studies. All the formulations showed good results which were compliance with Pharmacopoeial standards. In-vitro drug release studies were carried out using USP XXII dissolution apparatus type II at 50 rpm with 900 ml phosphate buffer solutions (PBS) of pH 6.8, maintained at 37±0.5 0 C. The release kinetics was analyzed using the zero-order, first-order model equation, Higuchi’s square- root equation, and the Korsmeyer-peppas model. In vitro release studies revealed that the release rate decreased with increases in polymer proportion. Matrix tablets containing 15% guar gum (Formulation F2) were found to show good initial release (21.34% in initial hour) and allowed sustained release up to 12 hours. Mathematical analysis of the release kinetics indicated that the nature of drug release from the matrix tablets was dependent on polymer concentration and it was found to be diffusion coupled with erosion. The developed controlled release matrix tablets of lamivudine, with sustained release characteristics might be able to minimise the demerits of conventional therapy having lamivudine.