Vous êtes sur la page 1sur 10

The comparative release studies indicate that the release of active material was strongly effected by the method

of formulation. The dissolution profiles of the complexes were studied in different dissolution media with the aim of differentiating between the

dissolution behavior of the complexes. The dissolution characteristics of the complexes in Simulated Gastric Fluid (SGF) without pepsin pH .! was studied. The dissolution

studies revealed that all the formulations showed an increased disslution rate. However in case of SGF without pepsin pH .! "#.$ % and #&.'% of the active drug from the (neaded mixture ( ) ) (valdecoxib*H+ *,-.-/012) respectively was dissolved

after '$ minutes and '& minutes. similarly in SGF without pepsin pH .!3 '4.54% and #5.!% of the active drug of free6e dried (valdecoxib*H+*,-.-/012) respectively was dissolved after '$ minutes3 an compared to !5. % of the pure valdecoxib at #& minutes. /ncase of phosphate buffer (pH .7)3 #7.'% and #$. % of the active drug material of 8neaded mixture (valdecoxib*H+*,-.-/012) respectively was released with "$ minutes and &$ minutes 3 Similarly #&.!% and #5.!$% of the active drug material of free6e dried (valdecoxib*H+*,-.-/012) respectively was dissolved after && minutes and !& minutes as compared to !". % of pure valdecoxib at "$ minutes. The

improvement is the dissolution rate of the drug.cyclodextrin system may be attributed to the degree of crystallinity of the active material together with the increase in both the wettabililty and the solubility of the drug and a distinct difference in the dissolution rate of the prepared complexes in SGF (pH .!) and phosphate buffer (pH .7) could not be seen because of the absence of any strong ioni6able group in valdecoxib molecule.

9n the basic of all the above studies3 it was finally concluded the maximum complex formation was achieved by 8neading method in a molar ratio ) with both -/012 and H+*,- as the complexing agent. Declaration

/ here by declare that this thesis entitled :/mproved -elivery of ;aldecoxib by <sing cyclodextrin -erivatives= embodied in this thesis was carried by me during the academic session !&&!*!&&7 in the -epartment of +harmaceutics3 Faculty of +haramcy3 >amia Hamdard (Hamdard <niversity) 3?ew -elhi3 <nder the direct supervision and outstanding guidence of -r. 0ushir @li and -r. sanAula 2aboota 3 -ept. of +harmaceutics3 Faculty of +harmacy3 >amia Hamdard3 ?ew -elhi. The extent and sources of information are derived from the existing literature and have been indicated throughout the thesis at the appropriate place. The wor8 is original and has not been submitted in part or full for any other -iploma or -egree of this or any other <niversity. +.G9BC/SH@?(@C -epartment of +harmaceutics3 Faculty of +harmacy >amia Hamdard ?ew -elhi & &5!.

C.Shan8ar3 @sho8raA3 SG 8umar3 ,hayapathi3 G,S @nand3 ,howdhary3 Cachna3 ?itin(umar3 Cagibehson3 2havna3 Dashomathi3 @shuthosh3 ;inayagam3 ubaidullah3 muniraA3 2iAu3 Cahul>ain3 Eiar rahman3 Summit3 sudharshan3 Hrithesh3 @ravind3 ?itin3 (ousthuv3 Cafi3 +unnet3 @6har

SUMMARY & CONCLUSION ;aldecoxib is an currently approved selective ,9F*! inhibitor. The absorption of valdecoxib occurs at !.!$hr is reGuired to reach ,max. This present study is an attempt to develop a tablet consisting of H+ *,- and -/012 cyclodextrin inclusion

complex of the drug to increase its solubility and dissolution rate thereby decreasing the onset of action. Following conclusion can be drawn from the result obtained . H+H,- and -/012 forms ) !. Solid valdecoxib*H+*,inclusion complex with valdecoxib in solution.

and valdecoxib H -/012

inclusion complex was

successfully prepared by 8neading and Free6e drying method. Grinding and ?eutrali6ation method did not give complex complexation. 4. The complex formation resulted in improved solubility and dissolution rate. 7. The tablets prepared with ;aldecoxib*H+H,- and ;aldecoxib* -/012 complex also showed Significantly increased dissolution of the drug. $. The prepared tablets showed comparatively improved release of valdecoxib than the mar8eted preparation IvahJK (?icholas +iramal Ltd.) 5. The anti* inflammatory study results shows a significance increase in percentage inhibition value by complexes in comparison to pure valdecoxib.

Introduction:
Treatment of pain is multifaceted and therapy is based among multiple area on decreasing the subAect intensity and direction of the pain complaint3 and decreasing the potential for conversion of active pain to chronic pain (text 2oo8 of the drug and disease management M!&&&) reGuirements for $"). @ fast onset of action3 and fast relief are the drug

drugs that are used to manage pain.

Generally 3 medications for pain relief are available in the form of oral dosage forms3 and most commonly on tablets. The ultimate goal of tablet is to serve as a carrier for drug to reach the blood stream for distribution to its site of action. @fter oral ingestion3 the drug contained within a tablet reaches the blood stream it disintegrates in a G/ treat into fine particles under the influence of the digestive Auices. Then such dissolved drug absorbed by G/ membrane by passive diffusive mechanism. /n these3 the slowest step that control the overall rate and extent of appearance of intact drug in the systemic circulation is called rate limiting step. This rate*limiting step may vary from drug to drug. Thus3 for a drug that has a vary poor aGueous solubility 3 the rate at which the drug dissolve in the G/ fluids is often the slowest step and therefore exhibits a rateHlimiting effect on the drug bioavailbility [Venkateswarlu et al ! "###$. /mprovements in the solubility characteristics of such a drug brings about faster solubility in the G/ fluids and hence faster absorption and ultimately faster onset of action.

Mec&anis' o( Action ?S@/-s share a common mode of action3 namely inhibiting

cyclooxygenase (,9F) en6ymes that are involved in the synthesis of prostaglandins. N ?S@/-s -rug today ### @pr.O. There are two informs of ,9F en6ymes ) the and the inducible ,9F*!. ,9F* is involved in

constitutively expressed ,9F*

prostaglandin synthesis in the gastric mucosa3 platelets and 8idneys3 and inhibition of this en6yme by nonselective ?S@/-s is thought to be responsible for the damage to the gastric mucosa and antiplatelet activity associated with this class of drug. Furthermore3 the inhibition platelet function by nonselective ?S@/-s increase the increases the ris8 of bleeding in a preoperative setting. /n contrast3 ,9FH! is thought to primarily affect the generations of prostaglandin involved in inflammation. This drugs that selectively inhibit ,9F*! should supress inflammation without causing the gastric adverse effects associated with nonselective ?S@/-s or without increasing the ris8 of bleeding due to their lac8 of effects on platelet function )Dou*las O ! dru*s "##"+ " %# " ,recautions and Contradictions )Dru*s Dou*las # ! "##"+ /n some trials3 There are increased incidence of nausea. /n ,omparative trials with non selective ?S@/-s3 valdecoxib was shown to have no significant effects on the gastroduodenal mucosa or platelet functions. " %# - Ad.erse e((ects )Dou*las # ! Dru* "##"+

+lasma concentrations of vadecoxib were increased by 4&% in patients with moderate hepatic insufficiency and therefore3 the drug should be use with caution in patients with mild to moderate hepatic impairment )c&ild / 0u*& class 1+ ;aldecoxib is not recommended in patients with severe hepatic insufficiency clearance of valdecoxib is not significantly altered in patients with mild to severe renal impairment3 but because of the possible ris8 of worsening of renal function3 ;aldecoxib is not recommended for patients with advanced renal disease. Scannin* electron Microsco02 )S3M+ The Scanning electron micrographs of pure ;aldecoxib hydroxyl propyl *

cyclodextrin pure dimethyl *cyclodextrin and inclusion complexes prepared by different methods in ) molar ratio are shown in fig C- H" @lthough this techniGue is not conclusive for assessing the existence of a true inclusion compound in the solid state3 it can be of some utility to prove the homogeneity of the solid phases +ure valdecoxib is characteri6ed by the presence of crystalline particle of regular si6e. +ure H+*,also appears on crystalline particles without

a definite shape +ure -/012 appears an crystalline lumps.

/n the S10 of valdecoxib H+*,- physical mixture the cyclodextrin structure can be detected with scattered crystals of valdecoxib. /n the S10 of valdecixib*H+*,- complex prepared by 8neading method shown amorphous lumps P crystals of the drug are not seen indicating complex fomation. /n the S10 of valdecoxib H+*,- free6e dried complex small si6e particles tending is aggregation are observed suggesting the existence of and amorphous product. S10 of valdecoxib H+*,- complex prepared by ?eutrali6ation method3 shows crystalline lumps which indicates the incomplete or partial complex functions. The inclusion complex of valdecoxib with -/012 prepared by grinding method shown the presence of both the valdecoxib crystals and -/012 particles. S10 of valdecoxibH-/012 complex prepared by 8neading shows crystalline structure of cyclodextrin with scattered crystals of the drug seems that the intact

structure of cyclodextrin the drug has been affected and an amorphous picture appears beside the presence of pure compounds3 thus indicating incomplete or particle complex formation /n case of valdecoxibH-/012 free6e dried complex3 the crystalline structure of the valdecoxib is not visible but it shows the larger particle which indicates

the amorphous nature of the complex. /n the S10 of valdecoxib*-/012 complex prepared by ?eutrali6ation method3 shows large crystalline lumps which indicates the lesser or partial complex formation.

Therefore an overall conclusion can thus be made that maximum complex formation was achieved by free6e drying and also by method both in ;aldecoxib H+ * ,- .-/012 complexes .

,&ar'acolo*2 o( Valdeco4i5 <ses and administration (valde /?? BH9 -rug inform ##'). ;aldecoxib is used in the management of Cheumatoid arthritis and 9steoarthritis. ;aldecoxib also has been used in the treatment of pain associated with primary dysmenorrhea. ;aldecoxib is administered orally as a &mg tablet once daily for the management rheumatoid arthritis and osteo arthritis. 2ut recommended dose for the relief of pain associated with primary dysmenohea is 7&mg tablet once daily.