Rajiv Gandhi University of Health Sciences Karnataka
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|6.0 |BRIEF RESUME OF THE INTENDED WORK |
| |ENCLOSURE – I |
| |6.1 Need for the study |
| |The oral route remains the preferred route of drug administration due to its convenience, good patient compliance and low medicine |
| |production costs. In order for a drug to be absorbed into the systemic circulation following oral administration, the drug must be dissolved|
| |in the gastric fluids. The active pharmaceutical ingredient in a solid dosage form must undergo dissolution before it is available for |
| |absorption from the gastrointestinal tract1. |
| |The development of meaningful dissolution procedure for drug product with limited water solubility has been a challenge to both the |
| |pharmaceutical industry and the agencies that regulate them. These challenges include developing and validating the test methods, ensuring |
| |the method is appropriate discriminatory and addressing the potential for In vivo –In vitro studies2. |
| |Solubility behavior of a drug is one of the key determinants of its oral bioavailability. In recent years, the number of poorly soluble drug|
| |candidates has increased tremendously. The formulation of poorly soluble drugs for oral delivery presents a challenge to the formulation |
| |scientists. Oxicam derivatives of non-steroidal anti-inflammatory drugs (NSAID’S). The major drawback of these drugs is its low aqueous |
| |solubility that delays its absorption from the gastrointestinal tract 3, 4, 5, 6. |
| |Several techniques already exists, to enhance dissolution like particle size reduction via micronization or nano suspensions, conversion of |
| |a crystalline molecule to its amorphous state, complexation with suitable complexing agents, solid dispersions of drug in suitable carriers |
| |etc., for poorly soluble drugs. Apart from these techniques liquisolid compact technique is a feasible and novel approach to improve the |
| |dissolution of poorly soluble drugs by its immediate release dosage form3. |
| | |
| |The present study is to improve the dissolution of poorly soluble drug and to be released at gastric pH relevant to fed state by using the |
| |liquisolid compact technique. The USFDA, CDER guidelines, states that the use of USP – II paddle apparatus at 75 RPM stirring speed using pH|
| |7.4 phosphate buffer at 37 ± 0.50C up to 60 minutes prescribed for poorly soluble NSAID’S drugs. In this present study an attempt was made |
| |to study the drug release at pH 5 (Fed State condition). Hence, it is aimed to formulate Immediate release solid dosage form by adopting |
| |Liquisolid technique6, 7. |
| |ENCLOSURE – II |
| |6.2 Review of the literature |
| |Jennifer D, et al., suggested that development of dissolution methods for new chemical entities as per industry perspective 8. |
| |Robert AR, et al., suggested on dissolution test method development should consider the design and matrix (cohesive properties of formulated|
| |drug) of the dosage form as well as the physicochemical (intrinsic) properties of the active pharmaceutical ingredient. The dissolution test|
| |media selection should be justified for pH (recommended range pH 1.2–7.5) as well as surfactant type (ionic versus non-ionic) and level. By |
| |using in vitro dissolution tests, the industry generally seeks to establish In vivo–In vitro relationships 9. |
| |Ali N, et al., worked on liquisolid (LS) technique for dissolution rate enhancement of a high dose water-insoluble drug. Different LS |
| |formulations of Carbamazepine were accomplished by dissolving the drug in the non-toxic hydrophilic liquids and adsorbing the solution onto |
| |the surface of silica. The USP paddle method was used for all the In vitro dissolution studies. The rate of stirring was 100 ± 2 rpm. The |
| |dosage forms were placed in 900 ml of distilled water containing 1% (w/v) sodium lauryl sulfate (SLS) and |
| | |
| |maintained at 37 ± 0.50C. The formulations containing poly vinyl pyrrolidone (PVP) as additive has a better dissolution rate in comparison |
| |with conventional direct compressed tablet (DCT) 10. |
| |Rania HF, et al., investigated the In vitro and In vivo performance of the prepared liquisolid tablets containing Famotidine. It is held |
| |within the powder substrate in a solubilized, almost molecularly dispersed state, which contributed to the enhanced drug dissolution |
| |properties. All the tested liquisolid tablet formulations showed higher drug dissolution rate than the conventional, directly compressed |
| |tablets. In addition, the selected optimal formula released 78.36%. Further, the bioavailability study indicated that the prepared optimal |
| |liquisolid formula did not differ significantly from the marketed Famotidine tablets concerning Cmax, Tmax, and AUC (0–8) at P < 0.05 11. |
| |Spiro S, et al., worked on enhancement of Prednisolone dissolution properties using liquisolid (LS) compacts. The In-vitro release |
| |characteristics of Prednisolone, a very slightly water soluble glucocorticoid. The potential of liquisolid systems to improve the |
| |dissolution properties of water-insoluble agents was investigated using Prednisolone as the model drug. LS compacts demonstrated |
| |significantly higher drug release rates, in different dissolution media and volumes, compared to tablets prepared by the direct compression |
| |method 12. |
| |Amal AE, et al., carried out liquisolid Systems to improve the dissolution of Furosemide. This study was to enhance the in vitro dissolution|
| |properties of the practically water insoluble loop diuretic Furosemide, by utilizing liquisolid technique. The results shown that all |
| |formulations exhibited higher percentage of drug dissolved in water compared to that at acidic medium. Liquisolid compacts containing |
| |synperonic PE/L 81 demonstrated higher release rate at the different pH values 13. |
| | |
| |Amrit BK, et al., carried on improve Fenofibrate dissolution through its formulation into liquisolid tablets and then to investigate In |
| |vitro performance of prepared liquisolid systems. Enhanced drug release profiles due to increased wetting properties and surface of drug |
| |available for dissolution was obtained in case of liquisolid tablets 14. |
| |Sanjeev G, et al., worked on In vitro dissolution property of slightly water soluble Bromhexine hydrochloride was improved by exploring the |
| |potential of Liquisolid (LS) system. The In vitro release pattern of LS compacts and directly compressed tablets were studied using USP-II |
| |apparatus. The drug release shows significant benefit of LS in increasing wetting properties and surface area of drug available for |
| |dissolution. From this study it concludes that the LS technique is a promising alternative approach for improvement of dissolution property |
| |of water-insoluble drugs 15. |
| |Ali N, et al., worked on potential of liquisolid systems to improve the dissolution properties of a water-insoluble agent (Indomethacin) was|
| |investigated. Propylene glycol as vehicle produced higher dissolution rates in comparison with other formulation containing PEG 400 or Tween|
| |80 of the same concentration 16. |
| |ENCLOSURE – III |
| |6.3 Objectives of the study |
| |The specific objective of this study is to formulate and evaluate the liquisolid tablet of oxicam derivative with an aim. |
| |To increase the solubility of poorly soluble drugs. |
| |Simplicity of preparation and low cost. |
| |To minimize excipients in formulation compare with other formulations. |
| |To increase the therapeutic efficacy of drug. |
| |Novel, feasible and promising approach in tablet technology. |
| |Study the statistical significance of the evaluation parameters. |
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| | |
| |MATERIALS AND METHODS |
| |Materials: |
| |Drug : One of the NSAID’s (oxicam derivatives) such as Meloxicam, |
| |Piroxicam, Tenoxicam and Lornoxicam etc. |
| |Liquid Solvents : Non – Toxic Hydrophilic solvents like PEG (Poly Ethylene |
| |Glycol) -200, 400, Propylene Glycol, Glycerin and Tweens etc. |
| |Carriers : MCC (Microcrystalline Cellulose), Lactose etc. |
| |Coating agents : Silica (Amorphous) etc. |
| |Additives : PVP (Poly Vinyl Pyrrolidine), HPMC ( Hydroxy Propyl |
| |Methyl Cellulose) etc. |
| |Superdisintegrants : Crospovidone, sodium starch glycolate, Croscaramellose etc. |
| |Method: |
| |To develop liquisolid tablets on the basis of optimized loading factor, the drug is first dissolved in non – toxic hydrophilic liquids and |
| |then absorbed on suitable carrier. Further mass is coated with silica and compressed into tablets by direct compression method. |
| | |
| |Evaluation: |
| |Compatibility study by Fourier Transform Infra Red (FTIR) |
| |Phase solubility studies as per FDA guidelines. |
| |Surface Morphology of liquisolid compact by Scanning Electron Microscopy (SEM) |
| |Solid state by Differential Scanning Calorimetry (DSC)/ Powder X – ray Diffraction (PXRD) |
| |To evaluate pre compression parameters such as flow property, drug content uniformity, bulk density, tapped density, hausener’s ratio and |
| |post compression parameters such as Hardness, weight variation, friability and disintegration. |
| |In – Vitro release & Release kinetic studies at gastric pH 5 (fed state condition). |
| |Validation of the developed dissolution method. |
| |Study the statistical significance of the evaluation parameters. |
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| |ENCLOSURE –IV |
| | |
| |7.1 Source of data |
| |1. Library: Bharathi college of pharmacy |
| |E-library: Bharathi college of pharmacy |
| |Practical data’s are obtained from laboratory-based studies. |
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|7.0 |ENCLOSURE-V |
| | |
| |7.2 Method of collection of data |
| |Data on drug was collected through literature survey and from physicochemical data base such as solubility in various solvents, pH of the |
| |drug solution and compatibility of the drug with various excipients. |
| |A) Preparation: |
| |Preparation of liquisolid tablets by direct compression method. |
| |B) Characterization: |
| |Compatibility study by FTIR and characterization of formulation by surface morphology |
| |by SEM, solid state by DSC/ PXRD. |
| |Prepared powder mass will be evaluated for |
| |Flow property |
| |Drug content uniformity |
| |Bulk density |
| |Tapped density |
| |Hausener’s ratio |
| |Prepared liquisolid tablets will be evaluated for |
| |Hardness |
| |Weight variation |
| |Friability |
| |Disintegration |
| |In - vitro dissolution studies at fed state pH |
| |Validation of the developed dissolution method |
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| |ENCLOSURE-VI |
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| |7.3 Does the study require any investigation or intervention to be conducted on patients or other humans or animals? If so, please mention |
| |briefly. |
| |-NOT APPLICABLE- |
| |7.4 Has ethical clearance been obtained from your institution in case of 7.3? |
| |-NOT APPLICABLE- |
| | |
| |ENCLOSURE – VII |
| |LIST OF REFERENCES |
| |Venkat BY, Adhikrao VY. Enhancement of solubility and dissolution rate of bcs class II pharmaceuticals by nonaquious granulation technique. |
| |Int J Pharm Res Dev 2010;1(12):08–20. |
| |Gowthamarajan K, Sachin KS. Dissolution testing for poorly soluble drugs: a continuing Perspective. Dissolution Technol 2010;17(2):24–32. |
| |Amal AE, Ngiik T. Effects of liquisolid formulations on dissolution of Naproxen. Eur J Pharm Biopharm 2009;73:373-84. |
| |Yadav VB, Yadav AV. Liquisolid granulation technique for tablet manufacturing: an overview. J Pharm Res 2009;2(4):670-4. |
| |rx |
| | |
| |US FDA Dissolution methods for drug products,[ |
| |cder/dissolution/dsp_SearchResults_Dissolutions.cf] |
| |Jennifer D, Johannes K. Pharmaceutical Dissolution Testing. United States of America: Taylor & Francis Group; 2005. p. 69 - 93. |
| |Robert AR, Cynthia KB, Hitesh PC, Beverly N, Brian RR. Acceptable analytical practices for dissolution testing of poorly soluble compounds. |
| |Pharm Tech 2004;28(12):56-65. |
| | |
| |Ali N, Yousef J, Baharak JN. Liquisolid technique for dissolution rate enhancement of a high dose water-insoluble drug (carbamazepine). Int |
| |J Pharm 2007;341:26–34. |
| |Rania HF, Mohammed AK. Enhancement of famotidine dissolution rate through liquisolid tablets formulation: In vitro and in vivo evaluation. |
| |Eur J Pharm Biopharm 2008;69:993–1003. |
| |Spiro S, Srinivas S. Enhancement of prednisolone dissolution properties using liquisolid compacts. Int J Pharm 1998;166:177–88. |
| |Amal AE, Babatunde A, Ebtessam AE and Sahar E. Liquisolid Systems to Improve the |
| |dissolution of furosemide. Sci Pharm 2010;78:325–44. |
| |Amrit BK, Indrajeet DG, Avinash HH, Pandurang ND and satish BB. Dissolution rate enhancement of fenofibrate using liquisolid tablet |
| |technique. Lat Am J Pharm 2009;28(2):219-25. |
| |Sanjeev G, Ravindra J. Liquisolid technique for enhancement of dissolution properties of bromhexine hydrochloride. Res J Pharm Tech |
| |2009;2(2):382–6. |
| |Ali N, Yousef J, Mohammad RS, Solmaz A. Liquisolid technique as a tool for enhancement of poorly water-soluble drugs and evaluation of their|
| |physicochemical properties. Acta Pharm 2007;57:99-109. |
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