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8 / BRIEF RESUME OF THE INTENDED WORK
6.1Need for the study
In recent years, in association with the progress and innovation in the field of pharmaceutical technology, there has been increasing effort to develop sustained release dosage forms for many drugs. Sustain release dosage forms have many advantages in the safety and efficacy over immediate release drug products, in which the frequency of dosing is reduced, drug efficacy is prolonged, and the intensity and incidents of adverse effects can be overcome or decreased.
Risperidone is a psychotropic agent belonging to the chemical class of benzisoxazole derivatives. The chemical designation is 3-[2-[4-(6-fluro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one. Risperidone is a solid, white to slightly beige powder. It is practically insoluble in water (2.8 mg/mL) and freely soluble in methylene chloride, and soluble in methanol and 0.1 N HCl.1 Risperidone being low soluble and high permeable belongs to class II of Biopharmaceutical Classification System (BCS). Risperidone is mainly used for the treatment of schizophrenia and other psychoses and in the short-term treatment of mania associated with bipolar disorder. The antipsychotic activity is reported due to its antagonistic activity at dopamine D2, serotonin (5-HT2), adrenergic (α1 and α2), and histamine (H1) receptors.2
Risperidone is administered orally or by deep intramuscular injection. The dose of risperidone is initially, 500micrograms in two divided doses, slowly increased in steps of 500micrograms twice daily, generally at intervals of not less than 1 week and the maximum dose of risperidone is 16 mg/day in divided doses. It is available in the conventional tablet form with 0.5 mg, 1 mg, 2 mg, 3 mg, and 4 mg. Risperidone is readily absorbed after oral doses, peak plasma concentrations being reached within 1 to 2 hours. It is extensively metabolised in the liver by hydroxylation to its main active metabolite, 9-hydroxyrisperidone (paliperidone), oxidative N-dealkylation is a minor metabolic pathway.2The absolute oral bioavailability of risperidone is 70%. Excretion is mainly in the urine and, to a lesser extent, in the faeces. Risperidone and 9-hydroxyrisperidone are about 90% and 77% bound to plasma proteins, respectively. The half life of risperidone is 3 hrs.1
Risperidone being an antipsychotic drug needs to be developed into sustained release dosage form, for maintaining therapeutic levels of effective treatment and thereby improves patient compliance. However it requires enhancement of solubility and dissolution rate, with simultaneous development into sustained release drug delivery systems.
6.2 Review of the study
Many attemptshave been made to increase therapeutic efficacy, decreased frequency of administration and improved patient compliance by developing sustained release dosage forms. Sustained release dosage forms are prepared using different techniques such as wet granulation, melt granulation, and direct compression. Using these techniques, different types of tablets for controlled release were prepared namely insoluble matrix tablets, bilayered tablets etc. The drug release mechanisms from such a system can be explained by diffusion, dissolution, erosion, surface desorption and combination of diffusion and dissolution.
Survey of literature indicates that extensive work was conducted in the development of sustained release dosage forms. The drugs studied are metformin4, tramadol5, ambroxol hydrochloride6, bupropion7, potassium chloride8, diclofenac sodium9, aspirin10, nicorandil11, nifedipine12, ofloxacin13, prednisolone14 etc.
Class II (BCS) drugs have low solubility, therefore designing of such drugs into sustained release dosage forms includes their solubility enhancement by addition of surfactants, wetting agents, dispersants and complexing agents (BCD). Class II drugs like nifedipine was designed into sustained release dosage forms in the presence of BCD and found to produce satisfactory results.12 Risperidone sustained release tablets are to be developed using various polymers by different techniques. Sustained release tablets after their preparation shall be subjected to different quality control tests.
6.3 Objective of the study
The objectives of the present investigations are:
1)Development of risperidone sustained release matrix tablets using different polymers and different techniques.
2)Characterization of risperidone matrix tablets including in vitro drug release and evaluation.
Materials and Methods
7.1 Source of data
The physicochemical and biopharmaceutical properties of risperidone are collected from the literature.
7.2Method of collection of data (including sampling procedure, if any)
a)Analytical method for the estimation of risperidone will be developed in simulated gastric fluid and/or simulated intestinal fluid.
b)Risperidone β cyclodextrin complexes will be prepared for solubility improvement.
c)Risperidone sustained release tablets will be prepared using different polymers such as sodium alginate, xanthan gum, ethyl cellulose, hydroxy propyl methyl cellulose, eudragit, etc.
d)The prepared tablets will be prepared for thickness, weight variation, content uniformity, hardness and friability etc.
e)In vitro evaluation of risperidone sustained release tablets for the release characteristics.
f)Statistical analysis of data obtained from the results.
7.3Does the study require any investigation or inventions to be conducted on patients or other human or animals? If so, please describe briefly.
No, Not applicable
7.4Has ethical clearance been obtained from your institution in case of 7.3?
Not applicable
LIST OF REFERENCES
  1. 27-09-2007
  2. 27-09-2007
  3. 01-10-2007
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  5. Malonne H, Sonet B, Streel B, Lebrun S,
    De Niet S, Sereno A, Vanderbist F. Pharmacokinetic evaluation of a new oral
    sustained release dosage form of tramadol. Br J Clin Pharmacol. 2004;57(3):270-8
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  7. Tzong-Shi Wang, I-Shin Shiah. Acute psychosis following sustained release bupropion overdose. Fuel cells in a changing world tenth grove fuel cell symposium.2007;25-7.
  8. Senel S,Capan Y,Dalkara T, Tnanç N,Hincal A. Aformulation, bioavailability, and pharmacokinetics of sustained-release potassium chloride tablets.Pharm Res.1991;8(10):1313-7(5).
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  11. ReddyKR, MutalikS, ReddyS. Once-daily sustained-release matrix tablets of nicorandil formulation and in vitro evaluation. AAPSPharmSciTech. 2003;4(4):61.
  12. Chowdary KPR, Kamalakara Reddy G. Complexes of nifedipine with β-cyclodextrins in the design of nifedipine SR tablet. Ind J Pharm Sci2002;2:142-6.
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