sustained release

Bosentan is a dual endothelin receptor antagonist important in the treatment of pulmonary artery hypertension (PAH). It is licensed in the United States, the European Union and other countries by Actelion Pharmaceuticals for the management of PAH under the trade name Tracleer®. Bosentan is used to treat pulmonary hypertension by blocking the action of endothelin molecules that would otherwise promote narrowing of the blood vessels and lead to high blood pressure. The aim of the present study was to develop sustained release formulation of Bosentan to maintain constant therapeutic levels of the drug for over 12 hrs. Various synthetic polymers were employed as polymers. Bosentan dose was fixed as 62.5 mg. Total weight of the tablet was considered as 200 mg. the tablets are prepared by employing direct compression method using 8mm punch. And the Polymers were used in the concentration of 31.5, 41.25, 62.5 mg concentration. All the formulations were passed various physicochemical evaluation parameters and they were found to be within limits. And the drug and excipient compatibility studies showed that there is no interaction between the drug and polymers employed in the formulation. Whereas from the dissolution studies it was evident that the formulation F3, F16 showed better and desired drug release pattern i.e., 98.15±0.06, 96.64±0.02 % respectively in 12 hours. the project work is successful in developing sustained release formulations of Bosentan.

The conventional dosage forms have the disadvantages like frequent administration, poor bioavailability, unpredictable doses etc. To overcome the problems of the conventional dosage forms, newer research in drug delivery systems directed towards a amalgamation of several technologies, leads to the development of in-situ oral gels, which extend the contact time and slows down the removal of the drug. To improve the bioavailability and to prevent rapid loss of drug, the drug can be formulated as oral in-situ gel using stimuli sensitive polymers. Gel dosage forms are successfully used as drug delivery systems to control drug release and protect the medicaments from a hostile environment. This review work gives information about oral diseases, in situ gel, approaches and polymers used for in situ gelation.

The present investigation is to Design and In-vitro evaluation of the sustained release matrix tablets of Glimepiride used for the treatment of type 2 diabetes mellitus. The Glimepiride (6mg) sustained-release (SR) matrix tablets were prepared by wet granulation method using different concentrations of hydrophilic and hydrophobic polymers. Such as Xanthumgum, Microcrystalline Cellulose, Povidone, Guargum, Magnesium Stearate, Pectin. The mechanism of action of glimepiride in lowering blood glucose appears to be dependent on stimulating the release of insulin from functioning pancreatic beta cells. The mixture of Glimipride powder was subjected to pre compression evaluation such as angle of repose, loose bulk density, tapped bulk density, hausarner’s ratio and compressibility index. The FTIR Spectrum is carried for the pure drug and for the optimized formula. This indicated that there was not any interaction between drug and polymer. All the formulations (F1-F12) were evaluated for weight variation, hardness, thickness, Friability, Content uniformity and invitro dissolution. The invitro dissolution studies were performed in pH 7.4 indicated that formulation F8 (Glimepiride and Guar gum in the ratio of 1:6) is the most success full formulation of this study and exhibited drug release 99.2% in 12 hr.  To investigate the drug-release kinetics, data were fitted to various kinetic models such as zero-order, first-order, Higuchi equation, Korsmeyer-Pappas equation, and Hixson–Crowell equation.

The present study focuses on developing sustained release matrix tablets of Ibrutinib aiming to increase the therapeutic efficacy, reduce the frequency of administration and to improve the patient compliance. Sustained release matrix tablets of Ibrutinib, were developed by using different drug polymer ratios HPMC phthalate, Eudragit L 100, Eudragit S 100 as matrix former. All lubricated formulations were compressed by direct compression and by wet granulation method. Compressed tablets were evaluated for uniformity of weight, content of active ingredient, friability, hardness, thickness, in-vitro dissolution, and swelling index. All the formulation showed compliance with pharmacopoeial standards. Among the different formulation, B8 showed sustained release of drug for 12 hours with 86.55% release. The selected formulation (B8) was subjected to stability studies for three months at 25°C/60% RH, 30°C/65% RH and 40°C/75% RH and showed stability with respect to release pattern and all physical parameters. The regression coefficient value of Higuchi plot was found to be 0.9925 that showed that drug was released by diffusion mechanism. The slope value of korsmeyer-peppas equation was found to be 0.5062 which indicating that drug was released by non-fickian release mechanism. The R2 value for Hixson Crowell plot was found to be 0.9919 which indicates that drug release was limited by drug particle dissolution rate and erosion of the polymer matrix. Thus, drug in combination with Eudragit S 100 were found to be effective in retarding the release of Ibrutinib.

The main objective of this research work was to formulate and evaluate the bi layer tablets of chlorzoxazone by using different polymers. Chlorzoxazone is centrally acting skeletal muscle relaxant. The tablets containing immediate releasing layer and sustained release layer. The polymers used are microcrystalline cellulose pH 102, sodium starch glycol ate, croscarmellose, povidone for immediate releasing layer, HPMC K 100 cps, K4cps, E15cps, carbomer 971P, and natural gums like guar gum, Xanthan gum for sustained drug release layer. The matrix tablets were prepared by direct compression and wet granulation methods. All the excipients are tested for compatibility with drug, which revealed that there was no physical and chemical interaction occurred. The Pre formulation parameters such as bulk density, tapped density, compressibility index and Hausner’s ratio were analyzed. The In-Vitro drug release studied were Performed in the USP dissolution apparatus- (paddle) using pH 1.2 HCL buffer and pH 6.8 phosphate buffer as dissolution media at 100rpm speed and temperature of 37oC ± 5oC. The sampling was done at periodic time intervals of 1.5, 3, 4, 6, 8, 10 and 12 hours and was replaced by equal volume of dissolution media after each withdrawal. The cumulative amount of drug release at different intervals is estimated using UV method. Based on the evaluation result the formulations F6 was selected as best formulation among immediate release and is used to compress with sustained release layer. Among all formulation FB8 formulation (HPMC K100m 88%) shown maximum release of 98.84% drug in 12th hour.

The present research paper focuses on designing not only the sustained release tablets of acyclovir to ensure time-dependent, sustained release formulation but also studying the effect of sodium alginate, Xanthan gum and HPMCV K15 on the in vitro release profile of the tablet. The initial release of drug from these matrices occurs by the drug dissolution in the water penetrated into the matrix. The overall drug release from these matrices is governed by hydration, gel layer formation and drug diffusion into the gel layer and to the dissolution media. The formulations ACL1 to ACL5 are containing 200mg of drug with a combination of different excepients. The drug release showed in ACL1 was 95.78%, for only 10hrs and ACL2 showed 90.66% within 11hrs because there was less presence of Xanthan Gum. The Acyclovir tablets of ACL3 showed 91.35% in 12hrs, ACL4 and ACL5 showed drug release of 95.33% for 8hrs and 95.85% for 9hrs. In further formulations the dose of Acyclovir was increased to 400mg ACL6 to ACL10 that are containing combination of excipients. The drug release for the formulations ACL6 showed a drug release of 97.44% for 10hrs and ACL7 showed a drug release 92.4% for 11hrs. From these twelve formulations it was concluded that increase in concentration of Xanthan Gum and Sodium alginate overrun the effect of HPMC K15. The dissolution characteristics allowed for drug to be released in a controlled manner, highlighting the importance for the correct selection of polymers according to their physical, mechanical and pharmacokinetic properties.

The present investigation was aimed at estimating the effectiveness of the edible mucilage of Borassus flabellifer fruit as a polymer in the development of a gastric floating dosage form of ranitidine HCl. Borassus flabellifer fruit mucilage, was shown to aid in the formulation of floating tablets. In the present study, it was used as a pharmaceutical excipient and its efficiency was compared with HPMC in the formulation of ranitidine HCl floating tablets. Sodium bicarbonate was used as a gas-generating agent, ranitidine HCl  tablets were prepared by direct compression method. The prepared tablets were evaluated for physicochemical parameters and found to be within range viz. hardness, swelling index, floating capacity, thickness, and weight variation. Further, tablets were evaluated for in vitro release characteristics for 12 hrs. All in all, the formulation F3 manifested a prolonged release of the active ingredient. The optimized formulation F3 followed higuchi’s mechanism. Based on the diffusion exponent (n) value, the drug release was found to be diffusion controlled. From the study, it was evident that the mucilage manifested all the characteristics of a good pharmaceutical excipient that can be used for the formulation of floating tablets.

The objective of this study was to investigate hydrogenated vegetable oil (Lubritab) and hydrogenated castor oil (HCO) as potential lipophilic binders in melt granulation process for the preparation of sustained release matrices of venlafaxine hydrochloride, a highly water soluble drug. The effect of concentration, type of polymer and method of preparation (direct compression of physical mixtures and melt granulation technique) were studied. Granules prepared by melt granulation method were evaluated for micromeritic properties, FT-IR, DSC, XRD and SEM. The compressed tablets were subjected to thickness, hardness, friability, mass variation test, drug content and in vitro release studies. The result of dissolution study showed that formulations containing drug: HCO (1:3 m/m) retarded drug release more than those containing drug: Lubritab (1:3 m/m) ratio. In conclusion, melt granulation technique was found to be more appropriate in retarding the release compared to compression of physical mixtures of drug and lipophilic binder. The study showed that HCO and Lubritab are the appropriate meltable binders that can be utilized as matrix-forming agent to sustained the release of highly water soluble drugs.

The present study aims at the formulation of a floating drug delivery system of an antiulcer drug nizatidine using different grades of HPMC (K100, K4M, K15M & K100M) and an effervescent agent i.e. sodium bicarbonate. It was found that the release rate of nizatidine from tablet formulations prepared from HPMC K100LV was very high as compared to that from formulations containing higher viscosity grades namely K4M, K15M and K100M. In the current study, it was also found that overall rate of drug release tends to decrease with increase in concentration of HPMC. These observations are in agreement with the results reported in literature i.e. with the increase in polymer concentration and viscosity grade, the viscosity of gel layer around the tablet also increases leading to enhanced diffusional path length for the drug to follow and thus limits the release of active ingredient.

Isoxsuprine hydrochloride, a β2 agonist used in peripheral vascular disease was formulated into sustain release matrix tablets, by wet granulation method using HPMC K15M as release retardant in different proportions and PVP K25 as a binder. The parameter optimized using 32 factorial designs. The tablets of all batches were evaluated for drug content, hardness, friability, weight variation and in vitro drug release profile. The dissolution profiles of formulated tablets were compared with a marketed product. The similarity factor (f2) was calculated to check the similarity with marketed product. Different dissolution models were applied to drug release data in order to evaluate release mechanisms and kinetics. Mathematical treatment of the in vitro drug release data suggests that, the drug release of all the formulations exhibited nearly zero-order kinetics, the release exponent n ranged from 0.69 to 0.8 indicate that drug release from the all batches occurred by non-Fickian diffusion mechanism (anomalous transport), i.e. the release is ruled by both diffusion of the drug and dissolution of the polymer. According to SUPAC guidelines the formulation containing combination of 25% HPMC K15M and 10% PVP K25 is the most similar formulation to marketed product.