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FORMULATION, CHARACTERIZATION AND INVITRO EVALUATION OF MUCOADHESIVE MICROCAPSULES OF PARACETAMOL


Mishra J*, Nayak S.K

College of Pharmaceutical Sciences, Puri, Odisha, India

Abstract

The present study involves the preparation and evaluation of mucoadhesive microcapsules of Paracetamol as the model drug to enhance the residence time in the body. The microcapsules were prepared with sodium alginate and ethyl cellulose using Emulsification-Solvent Evaporation Technique. The morphology and particle size of the microcapsules were detected by optical microscopy and SEM. The drug loading efficiency was found to be 54-75.77%.The mucoadhesion testing was done by using the freshly incised goat intestine. The swelling ability was found to be 6-8.9% and 4-7.9% in distilled water and 0.1N HCl respectively. The invitro release of drug exhibited more than 12hours duration. The microcapsules prepared were found to be free flowing.

Key Words: Mucoadhesion, Scanning Electron Microscopy microcapsules, Sodium alginate, Ethyl cellulose, Paracetamol.

INTRODUCTION 

Paracetamol in the form of oral tablets and gels1,2 gets rapidly absorbed from small intestine absorbed on administration. Mucoadhesive drug delivery systems increases the retention period of formulation in the body and thus prolongs the drug releases3,4.Sodium alginate and ethyl cellulose has been used to prepare microcapsules & microspheres individually which gives controlled released for various categories of drugs like zidovudine, glipizide5,6 etc. Paracetamol is a NSAID has a biological half life of 2-3 hrs only and also shows effects of liver damage and peptic ulceration7. In the present study, microcapsules are prepared by emulsification-solvent evaporation technique by using SA and EC and were evaluated for size, invitro drug release, drug loading efficiency, swelling ability and mucoadhesion.

MATERIALS AND METHODS

Materials

Paracetamol, Chloroform, Sodium alginate (SA) was obtained from Loba pharmaceuticals Ltd. (India). Ethyl cellulose (EC) was obtained from Central drug house Pvt.Ltd. (India). Sodium hydroxide pellets, Potassium dihydrogen phosphate, were obtained from Ranbaxy fine chemicals Ltd. (India).All other chemicals or reagents were of analytical grade.

A UV/ VIS spectrophotometer (Elico India Ltd.) was used for drug analysis.

Preparation of Microcapsules

Microcapsules were prepared by Emulsification-Solvent evaporation technique as stated by Simon et al 8.Two phases were prepared, an aqueous phase comprising of SA maintained at 400C for 10min and a dispersed phase comprising of EC in Chloroform containing Paracetamol.The dispersed phase was added to the continuous phase slowly by continuous stirring maintaining temperature at 400C till volatile solvent evaporated completely. The formed microcapsules were separated by vacuum filtration, air dried and kept in a dessicator. Various combinations of formulations were prepared varying the polymer ratio (Table 1) but best are reported.

Evaluation of Microcapsules

Size and Shape of Microcapsules

The particle size was determined using a optical microscope9 (Olympus NWF 10x, Educational Scientific Stores, India), fitted with an ocular and stage micrometer. The morphology was determined by using SEM (Scanning Electron Microscopy).

Loading efficiency10

Exactly 100 mg of microcapsules were weighed out and triturated and suspended in a minimal amount of phosphate buffer pH 7.4 and filtered through a whatman filter no.41. Drug content was analyzed spectrophotometrically at 249nm (Table 1).

Sorption Studies11

Around 500mg of the fully dried microcapsules were taken and placed in two different media ,distilled water and 0.1N HCl for 48 hours at room temperature and measured the increase in weight at the end of 48hours by the following formula,

Percent Water Sorption = Ws-Wd/Wd X100,

Where,

Ws is the weight of the Swollen device, Wd is the weight of Dry Device

Mucoadhesion Testing12, 13

The mucoadhesive property of the microcapsules was evaluated by an invitro adhesion and compared with that of a non bio adhesive material, ethylene vinyl acetate microcapsules as described by Chowdary et al13. Freshly excised piece of goat intestine were mounted onto two glass slides with cyanoacrylate glue with their mucous layer exposed to the external environment and one slide was placed at the base and the other was hung to one arm of the analytical balance. About 50 microcapsules were spread on the lower wet rinsed tissue specimen and placed in a water bath at 370C, pressed both the slides together with the microcapsules between them. To the other pan of the balance placed weights in ascending order till both the slides separated from each other. The test was performed for 30min in distilled water (Table 1).

In vitro release studies

Dissolution assays were carried out in triplicate for 12 hours at 37±0.50C using phosphate buffer,pH 7.4 as dissolution media for P1,P2,P3,P4 only. The tests were performed in an apparatus as described in USP which is USPXIII by taking 100 mg of microcapsules in the sample holder. At prefixed time (30min), 5ml of solution were withdrawn and spectrophotometrically assayed for the Paracetamol content (l =249 nm) (Elico India Ltd.).

RESULTS AND DISCUSSION

NSAIDS suffers from many disadvantages and to overcome those problems various techniques are applied to prolong the release. Micro encapsulation techniques are most famous in extending the release of NSAIDS14.The particle size increased with an increase in the polymer concentration and found to be 1-3mm(Table1) and shape is exhibited in Fig1. These results are in agreement with the observations made by Kim et al and Jeffery et al, where higher concentration of the polymer results in formation of large microcapsules15, 16.

 

Fig1.Scanning Electron Microphotograph of Paracetamol Microcapsules

With the increase in SA concentration the drug loading efficiency also increased and was found to 54-75.77%(Table1).These result is in agreement with the observations made by the research groups who have stated that the amount of uncoated drug decreases with an increase in the polymer concentration17,18.

Table 1: Composition and Characteristic of microcapsules of different composition 

Batch Code Polymer ratio Particle size(µm) Loading efficiency (%)
P1 1:1.2 1.12±0.05 54.56
P2 1:1.3 1.3±0.07 63.57
P3 1:1.5 1.5±0.09 69.67
P4 1:3 2.1±0.09 75.77
P5 1:1 1.05±0.05 47.67
P6 1:1.1 1.1±0.06 52.78
EVA —– —— ——

As the concentration of SA increased, the swelling ability and mucoadhesion (Table 2) also increased but swelling was more as 6-7.2% in case of distilled water and 4-7% in 0.1N HCl whereas mucoadhesion was highest for 0.1NHCl than in comparison to water and intestinal.This result is in confirmation with the reported study‑11.The results of mucoadhesion showed that as the pH of the medium was critical for degree of hydration, solubility and mucoadhesion of the polymers as reported by Ch’ng et al19.

Table 2:Mucoadhesion and swelling ability

Batch Code                    Swelling ability(%)          Mucoadhesion           testing (Pressure,N/m2)
Distilled water 0.1N HCl 0.1N HCl Distilled water Intestinal PH
Wd

(mg)

Ws

(mg)

% Wd

(mg)

Ws

(mg)

%
P1 500 536 6.7 500 520 4 0.0105 0.0078 0.007
P2 500 538 7.0 500 527 5.1 0.0149 0.0097 0.0078
P3 500 544 8.08 500 536 6.7 0.0194 0.0098 0.0084
P4 500 548 8.76 500 543 7.9 0.024 0.0109 0.0086
P5 500 515 2.9 500 513 2.5 ——– ——— ——–
P6 500 517 3.2 500 514 2.7 ——– ——— ———
EVA —– —– —- —– —– 0.0015 0.0014 0.0011

It is observed that drug release was slow and depended on the composition of the coat (Fig2) i.e. as the amount of polymer increased the drug release decreased significantly20.

Fig.2: Drug Release profiles from Paracetamol-EC/SA microcapsules.

 CONCLUSION

Thus, microcapsules with an outer coat of alginate for mucoadhesion over ethyl cellulose as inner core coat entrapping the water soluble/dispersible drugs can be prepared by solvent-evaporation technique .The prepared microcapsules showed good mucoadhesion property in an invitro test. Release of paracetamol from the prepared EC-SA microcapsules was considerably affected by concentration of the polymers used. Moreover the polymer ratio and pH of the medium also affected the mucoadhesion of the device and also the swelling capacity of the microcapsules.These mucoadhesive microcapsules are thus suitable for oral prolonged release of paracetamol.

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