Physicochemical In vivo Anti-Inflammatory effect of Tablet containing Fenoprofen

Shailendra Singh Narwariya, Suman Jain

School of Studies in Pharmaceutical Sciences, Jiwaji University, Gwalior.

*Corresponding Author E-mail: shailudbs1@gmail.com

ABSTRACT:

Fenoprofen, a potent nonsteroidal anti-inflammatory drug, is widely used for relief of pain in patients suffering from rheumatic diseases, migraine, sore throat and primary dysmenorrheal. However, this drug has many gastrointestinal side effects produced by its oral administration, such as gastric bleeding and peptic ulcer. These effects were responsible for non-compliance among patients, which ultimately results in treatment failure. The physicochemical properties of Fenoprofen, make it a suitable candidate for transdermal drug delivery, which can overcome the drawbacks of oral administration. In this sense, tablets have been proved to increase the cutaneous absorption of lipophilic drugs when compared to conventional drug delivery systems. The carrageenan test is highly sensitive to nonsteroidal anti-inflammatory drugs and has long been accepted as a useful model to determine the anti-inflammatory effects of natural products. In the present study the anti-inflammatory activity of Fenoprofen and superdisintegrant was investigated by experimental carrageenan animal model. In our study, the induction of carrageenan in the rat hind paw started off the vascular phase of inflammation which was characterized by temporary vasoconstriction and vasodilatation that generated an increase in the size of the edema for all groups.

KEYWORDS: Anti-inflammatory study, Fenoprofen, gels, In vitro permeation, microemulsion.

INTRODUCTION:

Inflammation is a physiological and biological response of vascular tissues against harmful stimuli such as pathogens, damaged cells, or irritants. It is a process which can be classified as acute or chronic. In acute inflammation, an initial response of the body against the harmful stimuli is initiated by movement of plasma and leukocytes from the blood to the injured site, where a local inflammatory process is developed. On the other hand, chronic inflammation is characterized by the increment in the type of inflammatory cells present at the site of inflammation. This sustained physiological response in time causes simultaneous destruction and healing of the injured tissue¹. Some examples of chronic inflammatory diseases are osteoarthritis, rheumatoid arthritis, degenerative joint disease, and ankylosing spondylitis.

These disorders are associated with constant pain episodes and require the intake of nonsteroidal anti-inflammatory drugs (NSAIDs) as therapeutic agents in long-term treatment. These drugs exert the inhibition of inflammation by blocking the action of both isoforms of the cyclooxygenase enzyme (COX), known as COX-1 and COX-2. COXs convert arachidonic acid into prostaglandin H2 which is then metabolized into various prostaglandins, prostacyclins, and thromboxanes, which are the molecular mediators that start the inflammatory process². The main problem related to these therapies is that they cause systemic side effects associated with gastrointestinal (GI), renal, and cardiovascular toxicity³. In particular, long-term NSAIDs therapies employed in the treatment of chronic inflammatory diseases produce GI toxicity due to the generation of gastric ulcers⁴. Fenoprofen, is a non-steroidal drug used as antiinflammatory, analgesic and antipyretic. It is used in the treatment of osteoarthritis, rheumatoid arthritis and ankylosing spondilytis. Though it is rapidly being absorbed after oral administration, it undergoes significant first-pass metabolism. It has a very short half life of about 2-3 h and is associated with gastro-intestinal side effects like nausea, gastric irritation etc. To extend drug action, to improve delivery of drug into systemic circulation, the present study was undertaken with the aim to develop and evaluate transdermal films of fenoprofen using various polymers like HPMC and EC, plasticizer like DBP⁵. Further the in vitro drug release was studied using d-limonene and oleic acid as permeation enhancers which belong to diterpene and fatty acids respectively. The formulation that showed promising result was further subjected for in vivo studies^6-8.

MATERIALS AND METHODS:

Drug and Chemicals:

Fenoprofen, thymol, camphor, ammonium bicarbonate were received as a gift from Medizan Laboratories and all the other ingredients used were of analytical grade.

Animals and treatment:

Healthy albino wistarrats strain of either sex weighing 190±10g were selected for the study. The animals were kept under 12:12 h day and light schedules with temperature between 18 to 20ºC. They were housed in large spacious hygienic cage during experimental period. Animals were allowed to free access to water and standard pellet diet up to the end of the study.

In vivo anti-inflammatory activity:

Experimental Design:

Animals were divided into 4 groups (n = 6/group). Group I was kept as normal untreated control (5ml/kg saline), group II received Carrageenan 0.1ml of 2% (w/v) along with saline, group III received standard drug Fenoprofen administered orally 1 h before carrageenan suspension administration, group IV received Carrageenan 0.1ml of 2% (w/v) along with Fenoprofen and Super disintegrant formulation orally for 7 consecutive days (orally). The last dose was administered 60min before the induction of inflammation. Subsequently, all animals received a subcutaneous injection of 0.1ml of 1% (w/v) carrageenan solution in the plantar region of the right hind paw to induce edema. The paw volume was measured initially and then at 60 min intervals for up to 4 h after the injection, using a vernier caliper.

Statistical Analysis:

Results are provided as Mean±SD (n=6). Results were analyzed statistically using one-way analysis of variance (ANOVA) followed by Bonferroni t-test. P<0.05 was considered as level of significance while comparison between groups.

Table: 1: Paw volume at different time intervals

S. No.	Group	Time (hrs)
S. No.	Group	1	2	3	4	% Inhibition
I	Normal Control (5ml/kg)	0.00±0.00	0.00±0.00	0.00±0.00	0.00±0.00	-
II	Carrageenan control (0.1 ml of 2% (w/v)	1.81±0.109	1.99±0.107	2.18±0.105	2.32±0.080	-
III	Fenoprofen	1.69±0.114^NS	1.30±0.100**	0.95±0.165**	0.46±0.124**	80.17
IV	Fenoprofen+Super disintegrant (SSG) formulation	1.50±0.081**	1.10±0.092**	0.87±0.091**	0.32±0.085**	86.20
V	Super disintegrant (SSG)	1.80±0.113^NS	1.85±0.107**	1.94±0.110**	1.98±0.094**	14.65

Values are expressed as MEAN±SD at n=6, One-way ANOVA followed by Bonferroni test, *P<0.050, **P<0.001 and ^NSP>0.001 compared to the negative control

Fig. 1: Paw volume at different time intervals

The carrageenan test is highly sensitive to nonsteroidal anti-inflammatory drugs and has long been accepted as a useful model to determine the anti-inflammatory effects of natural products. In the present study the anti-inflammatory activity of fenoprofen and super-disintegrant was investigated by experimental carrageenan animal model. In our study, the induction of carrageenan in the rat hind paw started off the vascular phase of inflammation which was characterized by temporary vasoconstriction and vasodilatation that generated an increase in the size of the edema for all groups⁹. The excipients such as surfactants, polymers, super-disintegrants and multifunctional fillers have been included in dosage forms to increase the apparent solubility of drugs. Sodium starch glycolate is widely used in oral pharmaceuticals as a disintegrant in capsule and tablet formulations. Disintegration occurs by rapid uptake of water followed by rapid and enormous swelling¹⁰. Sodium starch glycolate is modified starch with dramatic disintegrating properties and are available as explotab and primogel which are low substituted carboxy methyl starches. The mechanism behind is rapid absorption of water leading to an enormous increase in volume of granules result in rapid and uniform disintegration. From the data of in vivo studies, it was assumed that Group IV formulation containing Fenoprofen+ Superdisintegrant (SSG) formulation exhibited more significant inhibition comparing with the other groups include the control^11-14. This significant anti-inflammatory activity may be due to the synergistic action of Fenoprofen and Superdisintegrant (SSG) resulting in the better suppression of various inflammatory mediators in prostaglandin synthesis, cytokinins production and leucocytes migration. Hence, it can be concluded that the Sodium starch glycolate at 4% acts as a good super-disintegranting agent and shows promising additive anti-inflammatory activity with Fenoprofen in quick relief of pain¹⁵.

CONCLUSION:

The present study showed that tablet of fenoprofen had optimum thermodynamic stability, potential for in vivo permeation release rate and inhibition of inflammation. These properties can facilitate development of a cutting-edge strategy for transdermal delivery of fenoprofen using innovative formulations.

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Received on 29.07.2021 Modified on 12.09.2021

Research J. Pharm. and Tech 2022; 15(10):4413-4415.

DOI: 10.52711/0974-360X.2022.00739