6.
7. / BRIEF RESUME OF THE INTENDED WORK
ENCLOSURE - I
6.1 NEED FOR THE STUDY
.
The oral route of drug administration is the most common and preferred method of delivery due to convenience and ease of ingestion.Although the oral route of administration is preferred, for many drugs it can be a problematic and inefficient mode of delivery for a number of reasons ˡ.
Improving oral bioavailability of drugs those given as solid dosage forms remains a challenge for the formulationscientists due to solubility problems. The dissolution rate could be the rate-limiting process in the absorption of a drug from a soliddosage form of relatively insoluble drugs. Therefore, increase in dissolution of poorly soluble drugs by various techniques presents a challenge to the formulation scientists.There are some techniques available to improve the solubility of poorly soluble drugs, Such as Solid dispersions, Complexation, Micronization, Supercritical fluid process, polymorphs and Eutectic mixtures etc. In these solid dispersion and complexation methods are showing better result in improving the solubility and dissolution rate compared to other techniques 2.
The increase in dissolution rate of drug in both the physical mixtures and the solid dispersions was reported because of the enhanced wettability, hydrophilic nature of the carriers and possibility of reduced crystallinity of the drug of the drug in the formulations 3. Melt adsorption , hot melt, solvent evaporation, supercritical fluid precipitation, fluidized bed coating, spray drying and electrostatic spinning methods are some of the techniques reported for the preparation of solid dispersion4-7. The most commonly used inert carriers for solid dispersions include poloxamers, polyethylene glycol, hydroxyl propyl cellulose and poly glycolised glycerides etc.
Complexation also one of the method which enhances the solubility of poorly soluble drugs. Complexation is the association between two or more molecules to form a nonbonded entity with a well defined stoichiometry. Complexation relies on relatively weak forces such as London forces, hydrogen bonding and hydrophobic interactions.The complexation with cyclodextrins is used for enhancement of solubility.Three naturally occurring Cyclodextrinsare α-Cyclodextrin,
β-Cyclodextrin and γ- Cyclodextrin. Complexation can be done by various methods such as Physical blending method, Kneading method, Co-precipitation method, Solvent evaporation method, Spray drying method and Freezedrying method etc.Among these techniques spray drying is the most suitable for scale-up 8.
Etoricoxib (5- chloro- 2- [6- methyl pyridine- 3- yl] - 3- [4- methylsulfonylphenyl] pyridine) is a novel, second generation,selectiveCOX-2inhibitor,administeredorallyas a non-steroidal anti-inflammatory and analgesic drug 9. It is anoff-white,crystallinepowder,relativelyinsolubleinwater andfreelysolubleinalkalineaqueoussolutions. Therefore, improvement in solubility and/ or dissolution rate of poorly water-solubledrugmaybeachievedthroughtheformationof soliddispersions or complexation by spray drying technique. Spray-drying is a common technique used in pharmaceuticals to produce a dry powder from a liquid phase. Another application is its use as a preservation method, increasing the storage stability due to the water elimination.
The main aim of this project is increasing the solubility and dissolution rate of Etoricoxib by suitable methods such as solid dispersion ,complexation etc by spray drying technique.
ENCLOSURE - II
6.2 REVIEW OF LITERATURE:-

1.Punitha S et al., reported the enhancement of solubility and dissolution of Celecoxib by solid dispersion technique. The solubility and dissolution studies showed there is a possibility of improvement solubility of Celecoxib through solid dispersion with Urea 10.

2.Choudhary D et al., reported dissolution rate of Glipizide was increased from solid dispersion prepared by the kneading technique by using poloxamers without any physical and chemical interaction 11.

3.Dixit RP et al., reported the invitro and invivo advantages of surface solid dispersion of Celecoxib on super disintegrants. The technique provided an improvement in bioavailability of the drug12.

4.Charumanee S et al., reported the advantages and limitations and practical applicability of surface solid dispersion over other techniques. The authors were successful in improving the dissolution rate of Piroxicam by surface solid dispersion 13.

5.Kumar VK et al., reported the improvement of solubility and dissolution behaviour of the poorly soluble drug, Valsartan by solid dispersion technique using SMP (skimmed milk powder) as carrier14.

6.Adrian C et al., reported different method for preparation of solid dispersion techniques like hot mix method, co grinding, co precipitation and solvent deposition method for Ibuprofen. The increased dissolution rate could be attributed to a combination of faster dissolution from amorphous drug Ibuprofen, microcrystalline drug deposited on the carrier surfaces and polymer swelling15.

7.Torrado et al.,studied preparation, dissolution and characterization of Albendazole solid dispersion. The results showed enhancement of dissolution and the solubility coefficient of Albendazole 16.

8.Sammour et al., studied formulation and optimization of mouth dissolving tablets containing Rofecoxib solid dispersion. The study showed that the amorphization of Rofecoxib offered a better dissolution rate from its solid dispersion 17.

9.Kim et al.,studied preparation of a solid dispersion of Felodipine using solvent wetting method. The dissolution rate of felodipine from PVP, HPMC, and poloxamer by solid dispersion was markedly improved 18.

10.Hirasawa N et al., reported a method to prepare solid surface dispersion granules by granulation method using high-speed agitation granulator at the rate of 600 rpm with an agitator and 2400 rpm with chopper19.

ENCLOSURE – III
6.3OBJECTIVES OF THE STUDY
The main aim of this investigation would be to enhances the solubility of etoricoxib by suitable methods such as solid dispersion, complexation by using spray drying technique for improving their solubility and dissolution rate.
The individual objectives to be achieved include:
1)Selection of suitable carriers such as polymer, complexing agent for the formulation by the
solid dispersionsor complexation methods for spray drying technique.
2)Pre-formulation studies on the drug and the excipients selected.
3) Selection of suitable methods for the formulation by spray drying technique.
4)Evaluation of formulated spray dried product by suitable parameters.
5) Optimization of the formulation according to the needs.
6) Comparison of dissolution profiles of the formulated solid dispersion or
Complexation with marketed products.
7) Stability studies of the selected preparation.
MATERIALS AND METHODS
Material:
Drug: Etoricoxib
Carriers: Various suitable grades of Polaxamer, Polyethylene glycol, Hydroxy propyl cellulose and Poly glycolysed glycerise, various suitable lipid carriers and suitable complexing agents.
Method:
Solubility Enhancement of Etoricoxib by spray drying method.
ENCLOSURE - IV
7.1SOURCE OF DATA
I Review of Literature from:
  1. journals: such as
- International Journal of Pharmaceutical Sciences
-International journal of Biopharmaceutics
- International Journal of Research in Pharmaceutical and Biomedical Sciences
- Indian Journal of Pharmaceutical Sciences
- Journal of Pharmacy Research
B. Text book : The pharmacological basis of therapeutics
C. Martindale’s Extra Pharmacopoeia
D. Internet Browsing
E. J-gate@Helinet
F. East Point College Library
ENCLOSURE - V
7.2METHOD OF COLLECTION OF DATA
The physicochemical properties, of the drug will be collected from drug information center, various standard Books, journals, websites and other sources like research literature bases data such as Medline, Science Direct etc.
The stepsinvolved in the methodology are:
  1. Pre-formulation studies of the drug, complexing agentsand polymers for spray drying.
  2. Screening of solubility of complex or solid dispersion by phase solubility.
  3. Formulation of Solid dispersions or Complexation by spray drying technique using various carriers.
  1. The effect of these carriers and their ratios on drug release shall be studied by Dissolution study.
  2. Selection of effective carrier for enhancement of dissolution for Etoricoxib.
  3. Determine the characteristics of the selected product by Infra-Red spectroscopy (IR), Differential Scanning Calorimetry (DSC) and X-Ray diffraction (XRD) studies.
  4. Stability studies under ICH guide lines.
  5. Statistical significance of collected data.

ENCLOSURE - VI
7.3 Does the study require any investigations or interventions to be conducted on patients or other humans or animals? If so, please describe briefly.
------NOT APLLICABLE ------
7.4 Has ethical clearance been obtained from your institution in case of 7.3.
----- NOT APPLICABLE-----
8. / ENCLOSURE - VII
LIST OF REFERENCES
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  1. Prajati ST, Gohel MC, Patel LD. Studies to enhance dissolution properties of Carbamazepine. Ind J pharm Sci 2007;69(3):427-30.
  1. Pinnamaneni S, Das NG, Das SK, Formulation approaches for orally administered
    poorly soluble drugs. Pharmazie 2002; 57: 291 – 300
  1. BakhleSS,UpadhyeKP,DeshpandeSA,NagulwarVP, WadetwarRN.Effectofvariouscarriersonsolubilityof Rofecoxib.IndJPharm Edu2005;39(3):166-8.
  1. VamsiKM,GowriSD.Roleofsupercriticalfluidsinthe pharmaceuticalresearch-Areview.IndJPharmEdu Res2007;41(1):10-17.
  1. Karanth H, Shenoy VS, Murthy RR. Industrially feasible alternative approaches in the manufacture of solid dispersions: A technical report. AAPS Pharm Sci Tech 2006; 7 (4): 1-8.
  1. Kulthe VV, Chaudari PD. Solubility Enhancement of Etoricoxib by Solid Dispersions Prepared by Spray Drying Technique. Ind J pharm Edu Res 2011;45(3):248-58.
  1. RodriguesAD,HalpinRA,GeerLA. Absorption, metabolism, and excretion of Etoricoxib, a potent and selective cyclooxygenase-2 inhibitor, in healthy male volunteers.DrugMetabDispos2003;31(2):224–32.
  1. Punitha S, Kathikeyan D, Devi P and Vedha Hari BN. Enhancement of solubility and dissolution of Celecoxib by solid dispersion technique. J Pharm Sci 2009;1(2):63-8.
  1. Choudhary D, Kumar S, Gupta GD. Enhancement of solubility and dissolution of Glipizide by solid dispersion(kneading) technique. Asian J Pharm 2009;3(3):245-51.
  1. Dixit RP, Nagarsenker MS. In vitro and in vivo advantage of Celecoxib surface solid dispersion and dosage form development. Ind J Pharm Sci 2007; 69(3):370-7.
  1. Charumanee S, Okonoki S and Sirithunyalug J. Improvement of dissolution rate of Piroxicam by surface solid dispersions. CMU J 2004;3(2):77-84.
  1. Kumar VK, Arunkumar N, Verma PRP, Rani C. Preparation and in vitro characterization of Valsartan solid dispersion using skimmed milk powder as carrier. Int J Pharm Res 2009; 1(3):431-7.
  1. Adrian C, Peter Timins, Mingchu Lu, Robert T. Disorder and dissolution enhancement, deposition of Ibuprofen onto insoluble polymers. Eur J Pharm Sci 2005;26:288-94.
  1. Torrado S, Torrado J, Cadorniga R. Preparation, dissolution and characterization of Albendazole solid dispersion. Int J Pharm 1996;140:247-50.
  1. Sammour O.A, Hammad M.A, Megrab N.A, Zidan A.S. Formulation and optimization of mouth dissolving tablets containing Rofecoxib solid dispersion. AAPS PharmSci Tech 2006;7:1-9.
  1. Kim E, Chun M, Jang J, Lee I, Lee K, Choi H. Preparation of a solid dispersion of Felodipine using solvent wetting method. Eur J Pharm Bio 2006;64:200-5
  1. Hirasawa N, Ishise S, Miyata H and Danjo A. Application of Nivaldipine solid dispersion to tablet formulation and manufacturing using crospovidone and methylcellulose as dispersion carriers. Chem Pharm Bull 2004;52(2):244-7.