Formulation and Evaluation of Oxcarbazepine Sustained release Matrix tablets

 

Dr. Y. Krishna Reddy*, Gazala Nousheen

Department of Pharmaceutics, Nalanda College of Pharmacy, Jawaharlal Nehru Technological University, Hyderabad, Telangana.

 

ABSTRACT:

The aim of the present work is to develop and evaluate sustained release matrix tablets of Oxcarbazepine. Oxcarbazepine use as monotherapy or adjunctive therapy in the treatment of partial seizures in adults with epilepsy and as adjunctive therapy in the treatment of partial seizures in children ages 4-16 with epilepsy. Total 9 formulations were prepared trail batches. The formulation was evaluated for various pre compression and post compression parameters. All the formulations showed compliance with the pharmacopoeia standards. On the basis of evaluated parameters formulation F6 was considered to be best one. Formulation F6 containing polymer Ethyl cellulose showed 98.72% in-vitro drug release profile. The release data for formulation F6 was fitted to various mathematical models like zero order, first order, krosmeyer peppas andHiguchi model. It was observed that drug follows zero order model.

 

 

 

INTRODUCTION:

Ideal characteristic of the drug for the sustained release dosage form are;

·       Drug should have a shorter half-life as drug with a longer half-life are inherently long acting drugs.

·       Drug should be absorbed from large portion of gastrointestinal tract, since absorption must occur through the gut.

·       Drug should be having a good solubility profile to be a good candidate for sustained release dosage form.

·       Dose of the drug should not be too large, as a larger dose is to be incorporated into sustained release dosage form.

 

Oxcarbazepine for use as monotherapy or adjunctive therapy in the treatment of partial seizures in adults with epilepsy and as adjunctive therapy in the treatment of partial seizures in children ages 4-16 with epilepsy. The main objective of this study is to extend the drug release there by reducing the frequency of dosage.

 

MATERIALS:

Oxcarbazepine Provided by Sura Labs, Dilsukhnagar, Hyderabad. HPMC K-100, Ethyl cellulose, Sodiumcarboxy methylcellulose, Magnesium Stearate, Talc, Lactose was gift samples from SD Fine Chemicals Ltd Mumbai, India.

 

METHODOLOGY:

Preformulation parameters:

The various characteristics of blends Angle of repose, Bulk density, Tapped density, Carr’s index, tested as per Pharmacopoeia.

 

Formulation development of Tablets:

Oxcarbazepine and all other ingredients were individually passed through sieve no ¹ 60. All the ingredients were mixed thoroughly by triturating up to 15 min. The powder mixture was lubricated with talc. The tablets were prepared by using direct compression method.

 

 

Table No:1 Formulation composition for tablets

Ingrediants	F1	F2	F3	F4	F5	F6	F7	F8	F9
Oxcarbazepine	150	150	150	150	150	150	150	150	150
HPMC K-100	25	50	75	-	-	-	-	-	-
Ethyl cellulose	-	-	-	25	50	75	-	-	-
Sodiumcarboxy methylcellulose	-	-	-	-	-	-	25	50	75
Magnesium Stearate	5	5	5	5	5	5	5	5	5
Talc	3	3	3	3	3	3	3	3	3
Lactose	117	92	67	117	92	67	117	92	67
Total weight	300	300	300	300	300	300	300	300	300

 

Evaluation of post compression parameters for prepared Tablets:

The designed formulation tablets were studied for their physicochemical properties like weight variation, hardness, thickness, friability and drug content as per IP.

 

In vitro drug release studies:

Dissolution parameters:

Apparatus                     -         USP-II, Paddle Method

Dissolution Medium     --  0.1 N HCl, p H 6.8 Phosphate buffer

RPM                             --        50

Sampling intervals -- 0.5, 1, 2, 3, 4, 5 ,6, 7, 8, 10, 11, 12 (hrs)             

Temperature-- 37°C + 0.5°c

 

Application of Release Rate Kinetics to Dissolution Data:

The obtained data were fitted into zero-order, first order, Higuchi and Korsmeyer-Peppas release model to analyze the mechanism of the drug release.

 

 

RESULTS and DISCUSSION:

Preformulation parameters of powder blend:

Table No:2 Pre-formulation parameters of Core blend

Formulation code	Angle of repose (Ө)	Bulk density (gm/cm3)	Tapped density(gm/cm3)	Carr’s index (%)
F1	27.12±1.64	0.289±0.003	0.317±0.012	9.779±1.35
F2	27.35±1.79	0.278±0.005	0.309±0.010	11.15±1.34
F3	25.78±1.54	0.268±0.006	0.304±0.015	11.84±1.31
F4	27.25±1.56	0.282±0.004	0.312±0.011	9.615±1.37
F5	28.47±1.72	0.272±.0005	0.301±0.013	9.634±1.34
F6	25.67±1.84	0.250±0.005	0.285±0.012	12.28±1.29
F7	26.86±1.49	0.291±0.003	0.316±0.011	7.911±1.36
F8	27.21±1.25	0.262±0.004	0.292±0.014	10.27±1.39
F9	25.20±1.31	0.287±0.003	0.308±0.016	6.818±1.37

All the values represent n=3

 

Tablet powder blend was subjected to various pre-formulation parameters. The pre formulation parameters values indicates that the powder blend has good flow properties.

 

Quality Control Parameters For tablets:

Table No:3 In vitro quality control parameters for tablets

Formulation codes	Average Weight (mg)	Hardness(kg/cm2)	Friability (%loss)	Thickness (mm)	Drug content (%)
F1	297.22	4.6	0.24	2.26	99.12
F2	298.45	4.8	0.31	2.28	98.26
F3	296.31	4.2	0.28	2.19	97.35
F4	299.84	4.5	0.19	2.22	99.22
F5	294.36	4.7	0.22	2.34	99.19
F6	300.05	4.2	0.15	2.18	100.05
F7	299.63	4.4	0.17	2.31	98.56
F8	298.37	4.9	0.26	2.24	99.37
F9	299.41	4.5	0.22	2.26	97.28

 

Weight variation test:

The average weight of the tablet is approximately in range of 296.31 to 300.05 mg, so the permissible limit is ±7.5% (>300 mg). The results of the test showed that, the tablet weights were within the pharmacopoeia limit.

 

Hardness test:

The results showed that the hardness of the tablets is in range of 4.2 to 4.9 kg/cm², which was within IP limits.

 

Thickness:

The result showed that thickness of the tablet is raging from 2.18 to 2.34 mm.

 

Friability:

The average friability of all the formulations was less than 1% as per official requirement of IP indicating a good mechanical resistance of tablets.

 

Drug content:

From the drug content studies it was concluded that all the formulations were showing the % drug content values within 97.28 - 100.05 %.

 

All the parameters such as weight variation, friability, hardness, thickness and drug content were found to be within limits.

 

 

 

 

In Vitro Drug Release Studies:

Table No:4 In vitro drug release profile of Losartan potassium from F1 to F9

TIME (HRS)	F1	F2	F3	F4	F5	F6	F7	F8	F9
0	0	0	0	0	0	0	0	0	0
1	22.12	21.42	15.49	12.14	14.75	19.42	25.12	23.78	21.22
2	38.75	32.28	21.96	21.67	20.42	25.56	38.12	32.85	30.42
3	51.42	38.12	26.96	28.52	29.63	28.58	48.39	48.72	45.12
4	54.46	42.84	30.84	34.53	34.68	35.43	56.52	62.52	51.68
5	61.52	46.45	37.72	39.12	39.54	41.42	60.54	68.52	56.74
6	69.72	54.42	41.73	44.85	45.12	49.53	69.46	74.86	63.42
7	81.75	57.56	48.52	50.96	42.51	53.52	80.61	79.42	71.45
8	89.11	68.49	55.33	59.43	48.63	58.94	88.51	87.51	78.52
9	92.02	73.41	64.53	67.81	53.76	65.65	94.59	92.98	83.54
10	94.41	85.46	72.79	73.76	65.13	76.21	97.52	96.83	87.76
11	95.54	87.01	86.86	80.12	82.21	87.89		97.86	91.42

 

Fig No:1 Dissolution profile of Oxcarbazepine (F1-F9 formulations).

 

From the above results it was evident that the formulation F6 is best formulation with desired drug release pattern extended up to 12 hours.

 

Application of Release Rate Kinetics to Dissolution Data:

Table No:5 Release kinetics data for optimised formulation

CUMULATIVE (%) RELEASE Q	TIME (T)	ROOT (T)	LOG (%) RELEASE	LOG (T)	LOG (%) REMAIN	RELEASE RATE (CUMULATIVE % RELEASE / t)	1/CUM% RELEASE	PEPPAS log Q/100	% Drug Remaining
0	0	0			2.000				100
19.42	1	1.000	1.288	0.000	1.906	19.420	0.0515	-0.712	80.58
25.56	2	1.414	1.408	0.301	1.872	12.780	0.0391	-0.592	74.44
28.58	3	1.732	1.456	0.477	1.854	9.527	0.0350	-0.544	71.42
35.43	4	2.000	1.549	0.602	1.810	8.858	0.0282	-0.451	64.57
41.42	5	2.236	1.617	0.699	1.768	8.284	0.0241	-0.383	58.58
49.53	6	2.449	1.695	0.778	1.703	8.255	0.0202	-0.305	50.47
53.52	7	2.646	1.729	0.845	1.667	7.646	0.0187	-0.271	46.48
58.94	8	2.828	1.770	0.903	1.613	7.368	0.0170	-0.230	41.06
65.65	9	3.000	1.817	0.954	1.536	7.294	0.0152	-0.183	34.35
76.21	10	3.162	1.882	1.000	1.376	7.621	0.0131	-0.118	23.79
87.89	11	3.317	1.944	1.041	1.083	7.990	0.0114	-0.056	12.11
98.72	12	3.464	1.994	1.079	0.107	8.227	0.0101	-0.006	1.28

 

 

Fig No:2 Zero order release kinetics graph

 

Fig No:3 Higuchi release kinetics graph

 

Fig No:4 Kars mayer peppas graph

 

Fig No:5 First order release kinetics graph

From the above graphs it was evident that the formulation F6 was followed Zero order release kinetics mechanism.

 

CONCLUSION:

Oxcarbazepine sustained release matrix tablets were successfully prepared by using various polymers to retard the release and achive the retard dissolution profile. It concluded from the present study that slow and controlled release of Oxcarbazepine over a period of 12 hrs was obtained from formulation F6 using Ethyl cellulose. The drug release kinetics revealed Zero order release kinetics pattern. Formulation and evaluation of sustained release matrix tablets of Oxcarbazepine was found to be satisfactory.

 

АCKNOWLEDGEMENT:

Thе Authors Arе Thankful to Sura Labs, Dilshukhnagar, Hydеrabad for providing thе nеcеssary facilitiеs for thе rеsеarch work.

 

REFERENCES:

1.     Singh Surya Pratap, Soni Shankar Lal, Khinchi Mahaveer Prasad, Gulia Ritu, Namdev Abhisek. A Brief Review on Sustained Release Matrix Tablets of Baclofen. 01/12/2014.

2.     Chien Y. W., “Novel Drug Delivery System” (IInd Edn), Revised and Expanded, 1992, p.no.139-140.

3.     Remington, “The Science and Practice of Pharmacy”, 20th Edn, Vol. I, p.no.903-913

4.     Brahmankar D. M. and Jaiswal S. B. in “Biopharmaceutics and Pharmacokinetics”, "A Treatise,” Vallabh Prakashan, 1st edn, 1995, p.no. 347- 352.

5.     Lee V. H., Robinson J. R. in, “Sustained and Controlled Release Drug Delivery System” Marcel Dekker, New York, p.no. 71-121.,138-171.

 

Accepted on 01.05.2020      ©Asian Pharma Press All Right Reserved