Formulation and in-vitro Evaluation of Indomethacin Microcapsules

T.V.Rao¹*, S.Vidhyadhara² and Dr. Prof. K.R.S. Sambasivarao³

¹Associate Professor, Bapatla College of Pharmacy, Bapatla, Guntur District, Andhra Pradesh- 522101

²Professor and Principal, Chebrolu Hanumaiah Institute of Pharmaceutical Sciences, Guntur, Andhra Pradesh.

³Head Deportment of Biotechnology, Achrya Nagarjuna University, Gunter, Andhra Pradesh.

ABSTRACT:

The objective of this research was to formulate and evaluate the Indomethecin microcapsules for controlled drug delivery by emulsification solvent evaporation technique, employing Eutragit RL100 as coating material. Prepared microcapsules were evaluated for average particle size, Flow properties, Microencapsulation efficiency and invitro drug release studies. The drug-polymer interaction evaluated by FT-IR spectroscopy. They were found to be discrete, free flowing high percentage of drug entrapment efficiency and also retard the release for 12 hrs. The in vitro dissolution study confirmed that the formulations followed zero order kinetics and peppas release mechanism.

KEYWORDS: Indomethacin, Eudragit RL 100,MicroCapsues,FT-IR

INTRODUCTION:

Sustained /controlled release dosage forms are designed to achieve a prolonged therapeutic action by releasing the medication over an extended period of time by administration of single dose. Microencapsulation is one of the methods used to prepare these dosage forms.

Indomethacin, a non steroidal anti-inflammatory agent has a biological half life 2.6-11.2 hrs. Oral dose for adults was 25-50 mg, 2-3 times a day. To reduce the dosage frequency, controlled release formulations of Indomethacin were designed in the form of microcapsules for patient compliance and reduce adverse effects. The effect of polymer concentration on physical properties and drug release from the microcapsules were studied in the present investigation.

MATERIALS AND METHODS:

Indomethacin was a gift sample from Hetro Drugs Pvt. Limited, Hyderabad, India, Eudragit RL 100 from Central Drug House Private Limited, Methanol, Sodium hydroxide, potassium dihydrogen phospoate from Qualigens Fine Chemicals, Mumbai.

PREPARATION OF MICROCAPSULES^{2 :}

Microcapsules of indomethacin were prepared by an emulsification-solvent evaporation method employing ethyl cellulose as coating material.

Eudragit RL100 (1 gm) was dissolved in chloroform (20 ml) to form homogenous polymer solution, Indomethacin (1 gm) was dissolved in it and mixed thoroughly. The resulting mixture was then added drop by drop into a beaker containing 200ml of an aqueous mixture of sodium CMC (0.5%w/v) stirring at 1000 rpm for 2 hrs to emulsify the added dispersion as fine droplets. A REMI medium duty stirrer with speedometer (model RQT 124) was used for stirring, Stirring was continued until the evaporation of chloroform at room temperature to produce spherical microcapsules.

The microcapsules were collected by vacuum filtration and washed repeatedly with water and the product was then dried to obtain discrete microcapsules. In each case different proportions of core:coat ratio 5:1(MC₁), 3:1(MC₂), 1:1(MC₃), 1:3(MC₄), and 1:5(MC₅)were used to prepare microcapsules.

Preformulation studies

Drug- polymer compatibility studies;

FT-IR spectrophotometer used to study the interactions between drug and polymer and the spectrum was recorded in the wavelength region of 400-4000 cm.

Evaluation of Microcapsules:³

The prepared microcapsules were evaluated for the following parameters:

Size analysis, Angle of Repose, Bulk Density, Tapped Density, Carr’s Index, Hausner’s ratio, Drug Content, Drug Entrapment Efficiency and In-vitro dissolution studies.

Size analysis:

For size distribution analysis, different sizes from each formulation were separated by sieving using a standard sieves. The amounts retained on different sieves were weighed and mean particle size of the samples were calculated by the following formula

Where n = frequency weight

d = mean size

Angle of Repose:

The flow characteristics of microcapsules were studied by measuring the angle of repose employing fixed funnel method. The angle of repose was calculated by using the following formula.

h = height of pile,

r = radius of the base of the pile,

θ = angle of repose.

Bulk Density and Tapped Density⁴

Bulk density and tapped density were measured by using bulk density apparatus. The samples were placed in a 100ml graduated cylinder. The cylinder was fixed on the bulk density apparatus and timer knob was set for 100 tapings. Bulk density and tapped density were calculated from the following formulae.

Carr’s Index and Hausner’s ratio:

Carr’s index and Hausner ratio were determined from the tapped and bulk densities of a known weight of samples using a bulk density apparatus. The following formulas were used for calculating Carr’s index and Hausner’s ratio:

Microencapsulation Efficiency:⁵

Microcapsules of indomethacin (50 mg) were powdered and extracted with 50 ml of methanol. It was filtered and 1 ml of filtrate was taken and suitably diluted with phosphate buffer p^H 6.2 and the absorbance was measured at 318 nm. Microencapsulation efficiency was calculated using the following formula.

IN VITRO DISSOLUTION STUDY:⁶

Microcapsules [(22/44 mesh size, (535.5µm)] containing equivalent to 75 mg of indomethacin were packed in hard gelatin capsule. The release of Indomethacin from the capsules was studied in phosphate buffer of p^H 6.2 (900ml) using a United states pharmacopoeia (USP) type II dissolution apparatus with a rotating paddle stirrer at 50 rpm and 37±0.5 ⁰C. 5 ml samples were withdrawn through a filter (0.45µm) at different time intervals and assayed at 318 nm using a UV - Visible spectrophotometer. The drug release experiment was conducted in triplicate.

RESULTS AND DISCUSSION:

The present investigation was carried out on the formulation and evaluation of oral controlled release formulations of Indomethacin microcapsules, which is having a short biological half-life, meant for treatment of Rheumatoid Arthritis, Osteo Arthritis, and Ankylosing Sponglitis.

Indomethacin microcapsules were developed by emulsification - solvent evaporation method employing Eudragit RL 100 was coating material. The IR spectra for Indomethacin, Eudragit RL 100 and its physical mixture were shown in fig 1.1.The results revealed that no interaction was found between drug and polymer. The microcapsules were found to be discrete, spherical, size range of different batches of microcapsules was in the range of 531µm to 975µm. the angle of repose values ranges from 16.11 to 26.5.

TABLE:1.1 PHYSICAL PROPERTIES OF INDOMETHACIN MICROCAPSULES FORMULATED WITH EUDRAGIT RL 100

Formulation Code	Particle size (µm)	Angle of Repose(θ)	Bulk density (gm/cm3)	Compressibility Index (%)	Hausner’s ratio
MC1	254.01	28.54	0.175	28.25	1.91
MC2	354.54	22.75	0.245	26.42	1.35
MC3	410.45	19.05	0.342	22.81	1.28
MC4	475.25	18.62	0.468	19.53	1.22
MC5	531.31	15.47	0.524	16.12	1.19

TABLE 1.2: RELEASE KINETICS OF INDOMETHACIN MICROCAPSULES FORMULATED WITH EHYLCELLULOSE.

Formulation	Correlation coefficient values				Release rate constant (K0) (mg/hr)	Correlation coefficient (n)
	Zero order	First order	Matrix	Korsmeyer-Peppas
MC1	0.9988	0.8948	0.9404	0.9988	18.40	0.9379
MC2	0.9986	0.9725	0.93702	0.9982	16.24	0..9488
MC3	0.9990	0.9112	0.9210	0.9992	10.68	0.9883
MC4	0.9864	0.8204	0.9445	0.9962	6.24	0.9992
MC5	0.9985	0.9812	0.9212	0.9969	4.21	1.0143

FIG 1.1 FT IR ANALYSIS FOR (a) Indomethacin (b) Eudragit RL 100

(c)physical mixture of Indomethacin and Eudragit RL 100.

FIG.1.2. RELEASE PROFILES OF INDOMETHACIN MICROCAPSULES UDRAGIT RL 100 FORMULATED WITH E BY EMULSIFICATION SOLVENT EVAPORATION METHOD

It has been stated that, bulk density values less than 1.0 gm/ml, it was further supported by Carr’s index and Hausners ratio. It indicates microcapsules found to be Good flow characteristics reported in table1.1

The drug entrapment efficiency analysis showed that, the entrapment of drug within each batch of microspheres ranges from 60.24 to 96.80.

The in vitro drug release from the formulations was studied for 12h and the data fitted into the zero order, first order, Higuchi and Peppas models. The formulation MC4 core:coat (1:3) retard the release for 12h, further increment of the polymer concentration, i.e 1:5 (core:coat) retard the release more than 12h. As the amount of polymer increased, drug release was retarded. This is because particle size, surface area available for drug release. The drug release from the formulations was found to be Zero order kinetics and Peppas mechanism i.e n was found to be in the range of 0.9379 to 1.0143, formulation exhibiting the non-Fickian diffusion mechanism.

CONCLUSION:

Eudragit RL100 coated microspheres of Aceclofenac could be successfully developed by Emulsification solvent evaporation technique, it involves emulsification and removal of solvent. Microcapsules exhibited good controlled release characteristics and were found to be suitable for oral controlled release for 12hrs.

ACKNOWLEDGEMENTS:

The author express his gratitude to M/S Hetero Drugs Ltd Hyderabad for providing gift sample and also thankful to bapatla Educational Society, Bapatla College of Pharmacy Bapatla, for providing to carryout research work.

REFERENCES:

1. Shanmugam S, Cendil Kumar A, Verticheivan T, Manavalan R, Venkatappayya D, and Pandey., UV spectrophotometric method for the estimation of Indomethacin, Indian drugs., 16(2001)

2. K.P.R. Chowdary and B.L.R Madhavy, Asian Journal of chemistry, 22(7)5175-5180(2010)

3. D. Babay, A. Hoffmann. Biomedical 9(6)482-488,(1988)

4. Aulton ME, wells TI. Pharmaceutics: the science of dosage form design. London, 3^rd edition Churchill livingstone, 342(1988) .

5. Patil. S. Kasture PV., Journal of Pharmaceutical Research, 61, 24-28(1988)

6. K.P.R Chowadry, P. Mohaptra and Muralikrishna., Ind. J. Pha. Sci.., 68,497(2006)

Received on 05.11.2011

Accepted on 27.11.2011

© A&V Publication all right reserved

Research Journal of Pharmaceutical Dosage Forms and Technology. 4(1): Jan. - Feb., 2012, 44-47