{"id":872,"date":"2015-02-16T07:55:13","date_gmt":"2015-02-16T07:55:13","guid":{"rendered":"http:\/\/biomedpharmajournal.org\/?p=872"},"modified":"2020-04-25T08:19:04","modified_gmt":"2020-04-25T08:19:04","slug":"formulation-and-evaluation-of-extended-release-matrix-tablet-of-tramadol-hydrochloride-using-hydrophilic-polymer","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol2no2\/formulation-and-evaluation-of-extended-release-matrix-tablet-of-tramadol-hydrochloride-using-hydrophilic-polymer\/","title":{"rendered":"Formulation and Evaluation of Extended Release Matrix Tablet of Tramadol Hydrochloride using Hydrophilic Polymer"},"content":{"rendered":"

Introduction<\/h3>\n

The aim of oral sustained drug delivery system is to achieve a prolonged therapeutic effect by continuously releasing medicament over an extended period of time after administration of a single dose. Sustained release constitutes any dosage form that provides medication over an extended time period. In general, the sustained release dosage form is to maintain therapeutic blood or tissue level of drug for a prolonged period usually accomplished by attempting slow first order fashion.<\/p>\n

In recent years sustained release dosage forms continuous to draw attention in the field of research for improved patient compliance and decreased incidence of adverse drug reaction.<\/p>\n

Systems that are designed as prolonged release can also be considered as attempts at achieving sustained-release delivery. Repeat action tablets are an alternative method of sustained release in which multiple doses of drug are contained within a dosage form, and each dosage is related to a periodic interval. Delayed release systems, function by maintaining the drug within the dosage form for some time before release. Commonly the release rate of drug is not altered and does not result in sustained delivery once drug release has begun.<\/p>\n

Successful fabrication of extended release products is usually difficult & and involves consideration of physicochemical properties of drug, pharmacokinetic behavior of drug, route of administration, disease state to be treated and, most importantly, placement of the drug in dosage form total will provide the desired temporal and spatial delivery pattern for the drug.<\/p>\n

The slow first order release obtained by an extended release preparation is generally achieved by the release of the drug from a dosage form. In some cases, this can be achieved by retarding the release of drug from a dosage form and in some cases; this is accomplished by a continuous release process1<\/sup>.<\/p>\n

One of the least complicated approaches to the manufacture of sustained release dosage forms involves the direct compression of the blends of drug, retardant material and additives to form a tablet in which the drug is embedded in a matrix core of the retardant2<\/sup>. There are various methods for preparing matrix tablets, namely Direct compression, Wet granulation, Melt granulation, Response surface methodology etc. For pain and inflammation, anti-inflammatory agents should be frequently administered to control inflammation level, Tramadol (\u00b5 opioid) may be benifited to patients experiencing pain throughtout the dosing interval3<\/sup>.<\/p>\n

In the present study, matrix extended release tablets of Tramadol Hydrochloride were prepared using different polymers like Ethylcellulose, HPMC, Carbopol and Xanthum Gum resulting in less frequent fluctuations in plasma concentrations.<\/p>\n

Materials and Methods<\/strong><\/p>\n

Tramadol Hydrochloride was provided by Milton Labs (Pondycherry, India). HPMC was supplied by Rankem limited (India), Carbopol and Xanthum Gum provided by Himedia (India), magnesium stearate and aerosol were purchased from S.D. Fine Chemicals (India).<\/p>\n

Preparation and Characterization of matrices<\/em><\/strong><\/p>\n

A total of nine formulations of Tramadol Hydrochloride ER tablet were punched by direct compression method using different polymeric ratio of HPMC, Carbopol and Xanthum Gum, then subjected to preformulation studies like Angle of repose, Bulk density, Tapped density, Carr\u2019s Index and post compression parameters like thickness, Hardness, Weight variation, Friability, Drug content analysis and Invitro<\/em> dissolution studies.<\/p>\n

Determination of Drug content<\/strong><\/p>\n

Tramadol Hydrochloride matrix tablets were tested for their drug content. Twenty tablets were finely powdered; 400 mg of powder was accurately weighed and transferred to a 50 ml volumetric flask. Then the volume was made up with 0.1N HCl and shaken for 10 minutes to ensure complete solubility of the drug. The mixture was centrifuged (type: 2000, Clements, Rydalmere, Australia) and 10ml of the supernatant liquid was diluted 20 times with 0.1N HCl, and after centrifugation the absorbance was determined spectrophotometrically (UV-Visible 1240 CE, Shimadzu Corp, Kyoto, Japan) at 272.8 nm.<\/p>\n

\u00a0<\/strong>Invitro Drug Release Studies<\/strong><\/p>\n

The matrix tablets were subjected to the paddle dissolution method using 900ml of phosphate buffer solution PH<\/sup> 7.4 +<\/u> 0.2 as dissolution medium. The dissolution test was performed at 100rpm and temperature was set at 37 \u00b1 1\u00baC. At predetermined time intervals over an 8 hour period, 4 ml samples were withdrawn, centrifuged and assayed spectrophotometrically at 272.5 nm11<\/sup>. After each sampling, equal volume (4ml) of fresh Phosphate Buffer with the same temperature was replaced. All experiments were run 3 times, and the calibration curve specifications were y= 0.006X +<\/u> 0.005 (r2<\/sup> = 0.9998, n=9).<\/p>\n

Mechanism of drug release<\/em><\/strong><\/p>\n

To study the release mechanism, various dissolution models were applied to the invitro<\/em> release profiles of the best formulations. The kinetic models include zero order, first order, higuchi\u2019s and korsmeyer model4<\/sup>.<\/p>\n

Table 1:\u00a0<\/strong>Formulation Of <\/strong>Tramadol Hydrochloride <\/strong>Matrix Tablets Using Different Ratios Of Polymers (F1-F9).<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n
S.
\nNo.<\/strong><\/td>\n		INGREIDENT<\/strong><\/p>\n

(mg)<\/strong><\/td>\n

FORMULATION<\/strong><\/td>\n<\/tr>\n
F1<\/strong><\/td>\nF2<\/strong><\/td>\nF3<\/strong><\/td>\nF4<\/strong><\/td>\nF5<\/strong><\/td>\nF6<\/strong><\/td>\nF7<\/strong><\/td>\nF8<\/strong><\/td>\nF9<\/strong><\/td>\n<\/tr>\n
1<\/td>\nTramadol hydrochloride<\/td>\n100<\/td>\n100<\/td>\n100<\/td>\n100<\/td>\n100<\/td>\n100<\/td>\n100<\/td>\n100<\/td>\n100<\/td>\n<\/tr>\n
2<\/td>\nHPMC<\/td>\n50<\/td>\n–<\/td>\n–<\/td>\n30<\/td>\n20<\/td>\n30<\/td>\n20<\/td>\n–<\/td>\n–<\/td>\n<\/tr>\n
3<\/td>\nCarbopol<\/td>\n–<\/td>\n50<\/td>\n–<\/td>\n20<\/td>\n30<\/td>\n–<\/td>\n–<\/td>\n30<\/td>\n20<\/td>\n<\/tr>\n
4<\/td>\nXanthan Gum<\/td>\n–<\/td>\n–<\/td>\n50<\/td>\n–<\/td>\n–<\/td>\n20<\/td>\n30<\/td>\n20<\/td>\n30<\/td>\n<\/tr>\n
5<\/td>\nMCC<\/td>\n200<\/td>\n200<\/td>\n200<\/td>\n200<\/td>\n200<\/td>\n200<\/td>\n200<\/td>\n200<\/td>\n200<\/td>\n<\/tr>\n
6<\/td>\nAerosil<\/td>\n3<\/td>\n3<\/td>\n3<\/td>\n3<\/td>\n3<\/td>\n3<\/td>\n3<\/td>\n3<\/td>\n3<\/td>\n<\/tr>\n
7<\/td>\nMagnesium steareate<\/td>\n7<\/td>\n7<\/td>\n7<\/td>\n7<\/td>\n7<\/td>\n7<\/td>\n7<\/td>\n7<\/td>\n7<\/td>\n<\/tr>\n
<\/td>\nTotal Weight<\/td>\n360<\/td>\n360<\/td>\n360<\/td>\n360<\/td>\n360<\/td>\n360<\/td>\n360<\/td>\n360<\/td>\n360<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

Table 2:\u00a0<\/strong>Release Kinetic Data.<\/strong><\/p>\n

 <\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n
Formulation<\/strong><\/td>\nZero order<\/strong><\/td>\nFirst order<\/strong><\/td>\nHiguchi\u2019s equation<\/strong><\/td>\nKorsmeyer<\/strong><\/td>\n<\/tr>\n
F 1<\/strong><\/td>\n0.813<\/td>\n0.625<\/td>\n0.942<\/td>\n0.961<\/td>\n<\/tr>\n
F 2<\/strong><\/td>\n0.917<\/td>\n0.591<\/td>\n0.977<\/td>\n0.965<\/td>\n<\/tr>\n
F 3<\/strong><\/td>\n0.820<\/td>\n0.660<\/td>\n0.939<\/td>\n0.972<\/td>\n<\/tr>\n
F 4<\/strong><\/td>\n0.888<\/td>\n0.613<\/td>\n0.982<\/td>\n0.963<\/td>\n<\/tr>\n
F 5<\/strong><\/td>\n0.936<\/td>\n0.634<\/td>\n0.995<\/td>\n0.950<\/td>\n<\/tr>\n
F 6<\/strong><\/td>\n0.895<\/td>\n0.751<\/td>\n0.954<\/td>\n0.960<\/td>\n<\/tr>\n
F7<\/strong><\/td>\n0.819<\/td>\n0.631<\/td>\n0.929<\/td>\n0.959<\/td>\n<\/tr>\n
F8<\/strong><\/td>\n0.908<\/td>\n0.761<\/td>\n0.967<\/td>\n0.955<\/td>\n<\/tr>\n
F9<\/strong><\/td>\n0.881<\/td>\n0.690<\/td>\n0.971<\/td>\n0.969<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Results and Discussions<\/strong><\/p>\n

Drug Excipient Compatibility Studies were carried out which showed no interaction between the drug and the polymer. The pre compression parameters like angle of repose (230 <\/sup>to 270<\/sup>), bulk density (0.57 g\/ml to 0.66 g\/ml), tapped density (0.54 g\/ml to 0.65 g\/ml) and carr\u2019s index of (17.2-19.7) were found to be in satisfactory range. The post compression parameters like hardness was found to be in the range of 6.2 to 6.5 kg\/cm2<\/sup>, thickness was found to be 4.02-4.62 mm, weight variation (< 5%) and friability (1%) and drug content (>95%) complied with the IP standard. The invitro<\/em> dissolution studies were carried out in 0.1N HCl and PH <\/sup>7.4 Phosphate buffer for 24 hours and it was found that combination of HPMC and Carbopol showed a retarded release of 63.8% at the end of 12th <\/sup>hour and 98.24% at the end of 24th<\/sup> hour. The mechanism of drug release was diffusion coupled with erosion.<\/p>\n\n\n\n
\"Figure<\/td>\n\n

Figure 1:<\/strong>Pre-Compression Parameters.<\/strong><\/p>\n

Click here to View figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

 <\/p>\n\n\n\n
\"Figure<\/td>\nFigure 2:<\/strong>Carr\u2019s Index<\/strong><\/p>\n

 <\/p>\n

Click here to View figure<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n\n
\"Figure<\/td>\nFigure 3:<\/strong>Post-Compression Parameters<\/strong><\/p>\n

 <\/p>\n

Click here to View figure<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n\n
\"Figure<\/td>\nFigure 4:\u00a0<\/strong>Friability.<\/strong><\/p>\n

 <\/p>\n

Click here to View figure<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n\n
\"Figure<\/td>\nFigure 5:\u00a0<\/strong>Cummulative (%) Release Of Tramadol Hcl F1,F2,F3 <\/strong><\/p>\n

 <\/p>\n

Click here to View figure<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n\n
\"Figure<\/td>\nFigure 6:\u00a0<\/strong>Cummulative (%) Release Of Tramadol Hcl F4,F5 <\/strong><\/p>\n

 <\/p>\n

Click here to View figure<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n\n
\"Figure<\/td>\nFigure 7:\u00a0<\/strong>Cummulative (%) Release Of Tramadol Hcl F6,F7.<\/strong><\/p>\n

 <\/p>\n

Click here to View figure<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n\n
\"Figure<\/td>\nFigure 8: Cummulative (%) Release Of Tramadol Hcl F8,F9.<\/strong><\/p>\n

 <\/p>\n

Click here to View figure<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

Conclusion<\/strong><\/p>\n

It was concluded that different polymeric combination of Hydrophilic HPMC & Carbopol polymer resulted in extending the release from the polymeric core.<\/p>\n

Refrencess<\/b><\/p>\n

    \n
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    Introduction The aim of oral sustained drug delivery system is […]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[7],"tags":[],"class_list":["post-872","post","type-post","status-publish","format-standard","hentry","category-vol2no2"],"_links":{"self":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/872","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/comments?post=872"}],"version-history":[{"count":5,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/872\/revisions"}],"predecessor-version":[{"id":33018,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/872\/revisions\/33018"}],"wp:attachment":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/media?parent=872"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/categories?post=872"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/tags?post=872"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}