Research & Reviews in Pharmacy and Pharmaceutical Sciences
Menue-ISSN:2320-1215 p-ISSN: 2322-0112
e-ISSN:2320-1215 p-ISSN: 2322-0112
Sanjay R Patel1*,and Vipul P Patel2
Department of Pharmaceutics,KNV Pharmacy College,Metoda,Rajkot,Gujarat,India.
Department of Pharmaceutics,S.K. Patel College of Pharmaceutical Research and Education,Gujarat,India.
Received date: 11/08/2013Accepted date: 30/09/2013
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The speculation of this research was to observe whether Eudrajit L microspheres have the potential to serve as an oral carrier for peptide drugs like insulin. Eudragit L-100 based Insulin loaded Microspheres were prepared by quasi-emulsion solvent diffusion method with polysorbate 20 as dispersing agent in the internal aqueous phase (IAP) and PVA/PVP as stabilizer in the external aqueous phase. The production yield was found to be between 61-79% for PS1-PS4. In the first hour drug release of different Microsphere formulations SP1- SP4 was noted to be 19-29%. This may be attributed to the drug present in the pores of the Microspheres. The overall cumulative percent release for different Microsphere formulations PS1-PS4 at the end of eight hours was found to be 56-86 %.
Insulin,oral,Eudrajit L,microspheres,hypoglycemic.
Peptides show the widest structural and functional variation and involve to the regulation and maintenance of all biological processes. Application of formulated therapeutic proteins is very challenging and difficult task. The key to achievement of proteins as pharmaceuticals is to have in place an efficient drug delivery system that allows the protein drugs to gain access to their target sites at the right time and for proper duration. Four factors that must be considered in order to fulfill this goal are pattern of drug release,route of administration,fabrication of formulation and method of delivery [1]. The delivery of insulin by non-parenteral routes has gained significant attention over last two decades. The alternate routes explored are ocular [2,3],nasal [4],buccal [5,6],rectal [7],pulmonary [8,9] and oral [10,11]. Among all alternative routes of administration of insulin,the oral route offers maximum advantage in terms of patient compliance. However,there are several limitations of oral route. These include low oral bioavailability due to degradation in the stomach,inactivation and digestion by proteolytic enzymes in the luminal cavity,poor permeability across intestinal epithelium because of its high molecular weight and lack of lipophilicity [12,13,14,15,16,17,18]. Eudrajit L dissolves at pH above 6,thus it would liberate insulin in small intestine but it will be chances to destroy by trypsin and chymotrypsin [19,20,21,22,13]. Insulin loaded Eudrajit L microspheres made by quasi-emulsion solvent diffusion method,given orally with a permeation enhancer. Thus a polymer that would liberate the drug at above pH 6 appears to be suitable for oral insulin delivery. Eudrajit L is such type of a polymer. It is an anionic polymer synthesized from methacrylic acid and methyl methacrylate and it has a pH dependent solubility. It is slowly soluble in the region of the digestive tract When used to entrap insulin in microspheres,it is expected to protect insulin from degradation by gastric juice and allow it to be released in the region of the GIT of pH > 6 i.e. large intestine or colon where proteolytic enzymes are low in concentration [24,25,26].
Human insulin,Porcine insulin injection,Eudrajit L 100,Polysorbate 20,Poly vinyl alcohol,Poly vinyl pyrrolidone,Potassium dihydrogen phosphate,Ethanol,Dichloromethane,Isopropyl alcohol,Hydrochloric acid.
Eudragit RL-100 based Insulin loaded Microspheres were prepared by quasi-emulsion solvent diffusion method. The internal phase consisted of Eudragit RL-100 (200mg) and triethylcitrate (1% v/v,as plasticizer) dissolved in 5 ml dichloromethane. The drug was added to this with gradual stirring (500 rpm). The internal phase was then poured into 0.5% w/v polyvinyl alcohol (PVA,molecular weight 30,000-70,000) solution in water,the external phase. After 8 hour of stirring the Microspheres were formed due to removal of Dichloromethane from the system. The Microspheres were filtered and dried at 40°C for 12 hours [27,28]. The compositions of various microspheres formulations are given in Table 1.
Table 1: Composition of Eudragit L-100 based microspheres formulations
In-vitro release studies were carried out in USP basket apparatus with stirring rate 50 rpm at 37±0.5 0C. Initial drug release was carried out in 900 ml of 0.1N hydrochloric acid for 2 hours followed by phosphate buffer pH 6.8 for next 6 hour. Samples were withdrawn at regular intervals and analyzed spectrophotometrically at 249 nm [29]. All the readings were taken in triplicate. The same procedure was followed for in-vitro release studies of Insulin loaded Microspheres. The samples were analyzed at 420 nm. The in-vitro release data of Insulin loaded Microspheres are given in Table 2 - Table 5.
The different Microsphere formulations of Insulin were subjected to in-vitro release studies using USP XX1V dissolution assembly. It was observed that for each formulation the drug release decreased with increase in the amount of polymer. This may be due to the fact that the release of drug from the polymer matrix takes place after complete swelling of the polymer and as the amount of polymer in the formulation increases the time required to swell also increases. The release showed a bi-phasic pattern with initial burst effect. In the first hour drug release of different Microsphere formulations PS1- PS4 was noted to be 19-29%. This may be attributed to the drug present in the pores of the Microspheres. The overall cumulative percent release for different Microsphere formulations PS1-PS4 at the end of eight hours was found to be 56-86 %.
Table 2: In-vitro drug release data for formulation PS1
Table 3: In-vitro drug release data for formulation PS2
Table 4: In-vitro drug release data for formulation PS3.
Table 5: In-vitro drug release data for formulation PS4.
Insulin loaded microspheres Eudrajit L and conclude that proper concentration of polymer and emulsification agents give us better formulation and production yield. This may be due to the fact that the release of drug from the polymer matrix takes place after complete swelling of the polymer and as the amount of polymer in the formulation increases the time required to swell also increases.