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Development and Evaluation of Hydrodynamically Balanced System of Tramadol Hydrochloride By Using Chitosan And Locust Bean Gum

Development and Evaluation of Hydrodynamically Balanced System of Tramadol Hydrochloride By Using Chitosan And Locust Bean Gum

Development And Evaluation Of Hydrodynamically Balanced System Of Tramadol Hydrochloride By Using Chitosan And Locust Bean Gum

ABSTRACT

The main purpose of the study was development and evaluation of hydrodynamically balanced capsule of Tramadol HCl by using chitosan and locust bean gum as a natural polymer that prolongs the gastric residence time. Chitosan with different grade (low molecular weight, medium and high molecular weight) and locust bean gum were used as a drug release retarding agents. The hydrodynamically balanced capsule of tramadol HCl were prepared by ordered mixing technique. The concentration of both the polymers was optimized in order to achieve the sustained release of drug (TH) for 10 hours. Then the prepared capsules were evaluated for buoyancy test and in vitro drug release were performed. And other characterization analysis was also considered like FTIR study, DSC/DTG/TGA study and interaction study were also performed on the basis of characterization analysis. From these studies it was confirmed that there is no interaction observed between drug and excipient. The drug release studies shows that the retarding drug release pattern is dependent on the concentration and molecular weight of polymer as the concentration /molecular weight increases the retarding drug release pattern was also improved. And the synergistic action of retarding drug release was observed by the addition of another polymer i.e locust bean gum. Release pattern was fitted with the different kinetic model like Zero order, First order, Higuchi model and Korsmeyer peppas and it was concluded from the models that the drug release pattern obeys zero order model which signifies high therapeutic efficacy and minimum side effects.

Keywords: Tramadol HCl, Chitosan, Locust bean gum, Hydrodynamically Balanced System, Buoyancy, Gastric Residence Time.

Author details-Pravjot Kaur1* Surabhi Ghildiyal2 and Dr. Shashank Soni3

Corresponding Author Address-1Department of Pharmacy, Sardar Bhagwan Singh Post-graduate Institute of Biomedical Sciences and Research, Dehradun, Uttarakhand, India; E-mail: pravjotkaur@gmail.com

1Department of Pharmacy, Sardar Bhagwan Singh Post-graduate Institute of Biomedical Sciences and Research, Dehradun, Uttarakhand, India; E-mail: subighildiyal@gmail.com

2Amity Institute of Pharmacy, Amity University Uttar Pradesh, Lucknow, India; E-mail: ssoni@lko.amity.edu

INTRODUCTION

Oral route has been declared the most suitable and broadly acknowledged path of drug delivery system. Therefore oral controlled release dosage forms owes a remarkable benefit and this route is being considered as the remarkable point in the field of pharmaceutical sciences to achieve the set of goals of therapeutic advantages such as: reduced dosing frequency, better patient comforts and compliance, variation in the plasma drug level is less, Lesser total dose, reduced gastro intestinal tract side effects, improved safety and efficacy ratio.

Several difficulties has been arises in developing oral controlled release system for enhancing absorption and better bioavailability.

Difficulties include:

· Facing inability to target the drug dosage form in the area of desire in stomach.

· Drug absorption is a complicated process and owing many variables

· Rapid transit time of GIT can hinder the drug release behaviour in the absorption zone and minimises the safety and efficacy of the drug dose etc.

A novel drug delivery system was accomplish to overcome all such processed variables and one of the attempts is gastro retentive system. Gastro retentive drug delivery system is design in such way that by improve the gastric residence time of drug it resides in the gastric region for the numerous hours, by improving the gastric retention time it improves the absorption and bioavailability, decreases the drug waste and improve the solubility of drug which are less soluble in gastric pH environment (Sharma et al., 2014).

Gastro retentive drug delivery system also helps to provide a remarkable better availability of new product with new valuable therapeutic possibilities and substantial benefit for patients. Access of floating drug delivery system is most beneficial and commonly used because this system is most advantageous leads to gastric retention effervescent which liberates Co2 when comes to the contact with GI fluids and makes effort to float the dosage form. System having less density (<1.004 gm/cm³) than gastric fluid and hence it support the buoyant behaviour in the fluid and shows controlled release behaviour of drug dosage form. GI tract helps to maintain the efficient drug concentration for the extent of time in a systemic circulation. (Singh et al., 2011)(Aslam et al.,2014)

After the swallowing of the drug delivery dosage form it should be reside in the stomach and delivery of the drug in the controlled design to its absorption site for continuous release of drug.

1.1 ANATOMY OF STOMACH

Figure 1.1- Anatomy of stomach (Sabale et al., 2010)

1.2 CONCEPT OF HYDRODYNAMICALLY BALANCED SYSTEM

Gastric emptying process of the dosage form is tremendously a variable process and the ability of the dosage form to extend and maintain the gastric emptying time is a remarkable consideration, and to abide in the stomach for the extensive interval than conventional dosage form. Various difficulties arise to design the controlled systems with an aim of better absorption and improving bioavailability. Among this one of the major issues are to reside the drug dosage form in an aim area of gastrointestinal tract. Drug absorption is very complicated phenomenons and it subject to variable process because it is associated to the contact time with small intestinal mucosa. Therefore the transit time of small intestine is very important parameter for the drug absorption. (Sabale et al.,2010)(Jain et al.,2011)

Hydrodynamically balanced systems are design in such a way that by extending the gastric residence time of drug it can abide in the gastric area for several hours and significantly prolonging the gastric retention timeof drug and this enhanced the bioavailability, decrease the drug waste and modify the solubility of drug. With the action of extending the gastric retention time of delivery system is valuable for achieving therapeutic benefit for the drug substances.

By implementing various principles like flotation, expansion, sedimentation, mucoadhesion, or by modifying shape system the controlled retention time of drug dosage forms can be achieved. (Garg et al.,2008)

1.2 MECHANISM OF HYDRODYNAMICALLY BALANCEDS SYSTEM

Figure1.2-Working principle of hydrodynamically balanced capsule

(Nasa et al.(2010)

According to this principle, hydrodynamically balanced capsule is composed of drug and gel molding hydrocolloid polymer or a matrix forming polymer. After the swallowing of this drug dosage form it comes in the contact with gastric fluid and swells, it maintains the integrity of shape and its bulk density reduces less than 1 gm/ml.

Then the air trapped between the swollen cast and convey buoyancy to this dosage form. When this drug dosage form comes in the contact with aqueous medium the hydrocolloid polymer forms a gelatinous barrier and controls the diffusion rate of solvent in and drug out from the dosage form. When the drug dosage form which is consist of drug and mixture of hydrocolloid polymer, the capsule shell dissolves and the polymer swells lead to form a gelatinous barrier and shows buoyant behaviour in the gastric fluid for extend period of time.(Patil*et al.,2005)

1.6PROPERTIES OF POLYMER THAT ARE USED IN GASTRORETENTIVE DELIEVERY SYSTEM

1.6.1 Controlled drug release

When by the process of simple drug dissolution, by membrane control, by diffusion, by osmotic systems, by erosions, retardation mediated by ionic interaction the sustained release cannot be supplied. By the use of anionic polymeric excipient controlled release for the cationic drugs can be achieved. The relation between the chitosan and therapeutic agents can be more prominent by using polyanionic drug and depend on ionic cross linking in addition form a stable complex so that the drug can be released in more prolonged duration of time.

1.6.2 Mucoadhesive property

This property is mostly based upon its cationic character and sometimes the hydrophobic interactions. Various anionic polymer excipients like hyaluronic acid, carbine, polycarbophyl their mucoadhesive properties are weak. In order to achieve high mucoadhesive properties the polymer need to display high cohesive properties like adhesive bond or else abort within mucoadhesive polymer rather than in mucus gel case and polymer.

1.6.3 In situ gelling properties

In situ gelling property offers by the hydrogels containing polymer when their pH dependent hydaratability properties are demonstrated properly and these in situ gelling property was enhanced by the thiolation process.

1.6.4 Transfection enhancing properties

For small molecules where controlled drug release for ionic drugs can be developed and large polyanionic polymer molecules like DNA-based drugs and siRNA form stable complexes. Alike nanoparticles exhibit a positive zeta potential when there is a high ratio of cationic polymer. Due of these small particles and net positive charge endocytosis can be achieved when the size is below 100nm. Few of the polymer found to have l

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