Chapter.

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3. REVIEW OF LITERATURE

Review Of Literature

A Arunachalam et al (2010) developed Metoprolol Succinate and Telmisartan combination in a single dosage form. it enhanced the patient compliance and prolong cardiovascular system, Various polymers, such as hydroxy propyl methylcellulose K4M (HPMC- K4M), hydroxy propyl methylcellulose K100M (HPMC- K100M), MCCpH102, Lactose DCL 11, Bronopol, were studied. The HPMC- K4M was found to be best in controlling the release. Invitro dissolu-tion studies were carried out for all the bi-layered tablets developed using USP dissolution apparatus type 2 (paddle). Atul Kuksal et al (2006) prepared and characterized extended-release matrix tablets of zidovudine using hydrophilic Eudragit RLPO and RSPO alone or their combination with hydrophobic ethyl cellulose. Release kinetics was evaluated by using United States Pharmacopeia (USP)-22 type I dissolution apparatus. Scanning electron microscopy was used to visualize the effect of dissolution medium on matrix tablet surface. Furthermore, the in vitro and in vivo newly formulated sustained-release zidovudine tablets were compared with conventional marketed tablet (Zidovir, Cipla Ltd, Mumbai, India). The in-vitro drug release study revealed that either Eudragit preparation was able to sustain the drug release only for 6 hours (94.3% 4.5% release). Combining Eudragit with ethyl cellulose sustained the drug release for 12 hours (88.1% 4.1% release). B. S. Sudha et al (2010) evaluated hydrogenated cottonseed oil (HCSO) as a Extended release matrix for a freely soluble drug, tramadol. Hydrophobic matrix tablets of tramadol, was evaluated by compression of physical mixture of drug and wax, dispersion of drug in HCSO by hot fusion or solubilisation techniques. The method of preparation of tablet had a significant effect on drug release with higher release observed from direct compression matrices and slower release from matrix prepared by dispersion (hot-fused matrices). Durgacharan A et al (2008) evaluated Glyceryl monostearate and Stearic acid in formulation of extended release dosage form of water soluble drugs. It was decided to study the effect of these waxes at different drug: wax ratios, on the release profile of drug from matrix formulations prepared using Glyceryl monostearate, Stearic acid and both waxes in combination. The Extended release matrices of Verapamil HCl were prepared by melt granulation technique in different drug: wax ratios. Drug release was studied by using USP apparatus-I with pH 1.2 for one hour and pH 6.8 for seven hours. The drug release profile

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3compared with marketed formulation and specifications given in USP for extended release Verapamil HCl tablets. Frank w. et al (1994) characterized the release of drug from a wax matrix tablet under relatively mild agitation conditions. It was found that phenylpropanolamine hydrochloride was released from a typical wax matrix by a diffusion mechanism. After an initial rapid release of drug from the tablet, the amount dissolved was proportional to the square root of time. The advance of the solvent front into the tablet matrix was also proportional to the square root of time. Compression force was not a major factor affecting drug release. Data on drug release from a single tablet face compared to release from a totally exposed tablet indicated that drug release is proportional to the total surface area. Gbolahan Samuel et al (2007) studied the solubility of ibuprofen in Witepsol H15, a semisolid wax matrix. Higuchi release rates and Hyper DSC (high speed differential scanning calorimetry ); solubility values of 1520%, 18.6% and 12.7% w/w resulted from the three techniques, respectively. Microscopy was useful in additionally examining crystal size, shape and homogeneity. Release rate experiments showed that release from these formulations followed Higuchi kinetics with an inflection in release rate constant at the drug loading corresponding to drug solubility. Hyper DSC not only measured solubility but also determined the melting point of the formulation. The results from these three techniques correlated well, suggesting that the simpler techniques of microscopy or Hyper DSC are appropriate to determine the solubility in semi-solid pharmaceutical formulations. Hadi Mehrgan et al (2005) studied effects of various hydrophilic (HPMC and Carbopol 971) and plastic (Ethylcellulose and Eudragit RL100) polymers on the release profile of diltiazem HCl from matrix tablets were evaluated in-vitro. For this purpose, tablets containing 60 mg of diltiazem HCl along with various amounts of the aforementioned polymers were prepared using the wet granulation technique. The results showed that all the polymers used in this study could slow down the release of diltiazem HCl from the matrices prepared. This effect, except for HPMC, generally increased proportionately with the amount of polymer. HPMC imparted the best control over drug release and could sustain it for approximately 6 h. All the matrices prepared had a burst release initially; however, it was minimum with HPMCcontaining formulations. Fitting of release data to different kinetic models showed that HPMC-matrices conformed best to Hixson-Crowell model, 4 ethylcellulose-matrices to Higuchi and both Eudragit RL100 and Carbopol 971-formulations to either of HixsonCrowell, Higuchi and first-order kinetics.

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Hamdy Abdelkader et al (2007) investigated different types and levels of hydrophilic matrixing agents, including methylcellulose (MC), sodium alginate (Alg), and sodium carboxymethylcellulose (CMC), in an attempt to formulate controlled-release matrix tablets containing 25 mg baclofen. The tablets were prepared by wet granulation. Prior to compression, the prepared granules were evaluated for flow and compression characteristics. In vitro, newly formulated controlled-release tablets were compared with standard commercial tablets (Lioresal and baclofen). The excipients used in this study did not alter physicochemical properties of the drug, as tested by the thermal analysis using differential scanning calorimetry. The flow and compression characteristics of the prepared granules significantly improved by virtue of granulation process. Also, the prepared matrix tablets showed good mechanical properties Hiroyuki Kojima et al (2008) evaluated the feasibility of using a counter polymer in polyethylene oxide (PEO)/polyethylene glycol (PEG) polymeric matrices for the extended release of a large amount of highly water-soluble drug. PEO/PEG matrix tablets (CR-A) containing four drugs with different water solubilities were prepared to investigate the effect of drug solubility on the drug-release and diffusion properties of PEO/PEG matrices. Crosslinked carboxyvinyl polymer (CVP)/PEO/PEG matrix tablets (CR-B) containing a watersoluble drug, diltiazem hydrochloride (DTZ), were also prepared, and their in vitro characteristics were compared with those of CR-A. Their in vitro drug release properties were evaluated using a dissolution test, and the polymeric erosion and drug diffusion properties of the matrices were also calculated. Drugs with higher solubility in water were released faster for the CR-A. Hua-Pinh Uangs et al (1994) evaluated acrylic polymer-wax matrix system for oral sustained-release tablets of diphenhydramine HCI. A desirable release profile of diphenhydramine was achieved by incorporating Eudragit L in a carnauba wax matrix. In this polymer-wax system, carnauba wax maintained the integrity of the matrix, whereas Eudragit L slowly eroded in the matrix as the drug was released. Thus, the area-to-volume ratio of the tablet remained constant over the duration of the drug release. K. Raghuram Reddy et al (2003) developed once-daily sustained-release matrix tablets of nicorandil. The tablets were prepared by the wet granulation method. Etha-nolic solutions of ethylcellulose (EC), Eudragit RL-100, Eudragit RS-100, and polyvinylpyrrolidone were used as granulating agents along with hydrophilic matrix materials like hydroxypropyl methylcellulose (HPMC), sodium car-boxymethylcellulose, and sodium alginate. Ac-cording

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to the theoretical release profile calculation, a once-daily sustained-release formulation should release 5.92 mg of nicorandil in 1 hour, like conventional tablets, and 3.21 mg per hour up to 24 hours. The results of dissolution studies indicated that formulation F-I (drug-to-HPMC, 1:4; ethanol as granulating agent) could extend the drug release up to 24 hours. Mine O zyazc et al (2006) investigated the swelling and relaxation properties of lipid matrix on diffusional exponent (n). The second aim was to determine the desired release profile of metronidazole lipid matrix tablets. They prepared metronidazole lipid matrix granules using Carnauba wax, Beeswax, Stearic acid, Cutina HR, Precirol_ ATO 5, and Compritol_ ATO 888 by hot fusion method and pressed the tablets of these granules. Stearic acid showed the highest and Carnauba wax showed the lowest release rates in all formulations used. Swelling ratios were calculated after the dissolution of tablets as 9.24%, 6.03%, 1.74%, and 1.07% for Cutina HR, Beeswax, Precirol_ ATO 5, and Compritol_ ATO 888, respectively. There was erosion in Stearic acid, but neither erosion nor swelling in Carnauba wax, was detected. M.u. Uhumwangho et al (2006) prepared matrix granules of acetaminophen formed by a melt granulation process whereby the acetaminophen powder was triturated with the melted wax - goat wax, glyceryl monostearate or carnuba wax. The compressibility of the matrix granules and their admixture, with diluent granules (lactose, -cellulose or microcrystalline cellulose) was investigated. Matrix granules prepared by melt granulation with goat wax or glyceryl monostearate were too sticky and therefore did not flow at all. They were also poorly compressible (T values = 0.20MN/m2). By contrast the matrix granules formed with carnuba wax were free flowing (angle of repose, 18.60). Addition of the diluent further improved flowability slightly. The matrix granules (without a diluent) were readily compressible (T value, 1.79MN/m2). Addition of the diluent (80%w/w) reduced T values (MN/m2) slightly to 1.32 (lactose), 1.48 (-cellulose) and 1.74 (microcrystalline cellulose). Tablets of the matrix granules only, disintegrated rapidly within 3minutes. 6 Prajapati B.G et al (2010) developed hydrophilic polymer and hydrophobic polymer based matrix Losartan potassium Extended release tablet which can release the drug up to time of 24 hrs in predetermined rate. Formulation of Losartan potassium matrix tablet was prepared by the polymer combination in order to get required theoretical release profile. Influence of hydrophilic and hydrophobic polymer on Losartan potassium was studied. Formulated tablet were also characterized by physical and chemical parameters. In vitro release profile was check for 24 hrs to evaluate the SR matrix tablet of Losartan potassium.

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Ravouru Nagaraju et al (2009) prepared core-in-cup matrix tablets of Metoprolol succinate by wet granulation technique. Of all the investigated formulations, the optimized formulation of MS-09 followed zero-order kinetics of drug release. Trail on MS- 09 was formulated using 7.5% hydrogenated castor-oil (HCO) and 4% of hydroxyl propyl methylcellulose (HPMC K15M) with an objective to achieve a linear release profile for 24 h. There was no initial burst release, with 16.17% of drug released during the first hour and release was extended up to 24 hrs. Study of drug release kinetics was performed by application of dissolution data to various kinetic equations like zero-order; first order, Higuchi and Korsmeyer-Peppa

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