Formulation and Evaluation of Sotalol Gastrorententive Tablets

G. Swathi¹*, Krishna Bhavan Jyothi Kumari¹, Ramya Sri S²

¹Department of Pharmaceutics, Samskruti College of Pharmacy,

Affiliated to JNTUH University, Hyderabad 501301, Telangana, India

²Department of Pharmacy, University College of Technology,

Osmania University, Hyderabad – 500 007, Telangana, India

*Corresponding Author E-mail: swathipharmacyg@gmail.com

ABSTRACT:

The objective of this study was to formulate floating tablets (GRDDS) of Sotalol using direct compression method to increase its bioavailability and the gastric residence time of the dosage form. The Sotalol tablets were prepared by direct compression method. The tablets were prepared by using different types of polymers i.e.; Sodium CMC, Chitosan and Psyllium Husk which act as a release retardant polymer. Sodium bi carbonate (NaHCO₃) was used as a gas degenerating agent and MCC (Micro crystalline cellulose) was used as a diluent. The prepared formulation were subjected to some evaluation parameters like hardness, friability, weight variation, drug content, buoyancy property, drug release study etc. In the FT-IR study it was revealed that there is no interaction between the drug and excipients. The formulation which containing Chitosan polymer and Sodium bicarbonate shows good drug release pattern with less floating lag time and good floating duration.

The in vitro drug release pattern of Sotalol floating tablets was fitted to different kinetic models which showed the highest regression for Higuchi order kinetics. Thus, it can be concluded that the floating drug delivery system of Sotalol using the appropriate polymers in right amount may enhance the activity of the drug by prolonging the gastric residence time or reducing the floating lag time.

KEYWORDS: Sotalol and Floating Tablets.

INTRODUCTION:

The aim of drug delivery system is to afford therapeutic amount of drug to the proper site in the body to attain promptly and then maintain desired drug concentration. Theoral route is increasingly being used for the delivery of therapeutic agents because the low cost of the therapy and ease of administration lead to high levels of patient compliance.

More than 50% of the drug delivery systems available in the market are oral drug delivery systems^1-4. Gastric emptying of dosage forms is an extremely variable process and ability to prolong and control the emptying time is a valuable asset for dosage forms, which reside in the stomach for a longer period of time than conventional dosage forms. Several difficulties are faced in designing controlled release systems for better absorption and enhanced bioavailability. One of such difficulties is the inability to confine the dosage form in the desired area of the gastrointestinal tract. The relatively brief gastric emptying time (GET) in humans which normally averages 2-3 h through the major absorption zone, i.e., stomach and upper part of the intestine can result in incomplete drug release from the drug delivery system leading to reduced efficacy of the administered dose. Sustained releases are dosage forms that provide medication over an extended period of time. Controlled release denotes that the system is able to provide some actual therapeutic control⁵. Controlled release (modified release) dosage forms are growing in popularity. These more sophisticated systems can be used as a means of altering the pharmacokinetic behavior of drugs in order to provide twice or once a day dosage. This is achieved by obtaining a zero-order release from the dosage form. Zero-order release includes drug release from the dosage form that is independent of the amount of drug in the delivery system⁶.

MATERIALS AND METHODS:

Sotalol procured from Cipla Pharmaceuticals pvt limited, Hydrabad, Provided by Sura Labs, Dilsukhnagar, Hyderabad. Sodium CMC procured from Degussa India Ltd. (Mumbai, India). Chitosan procured from Arvind Remedies Ltd, Tamil nadu, India. Psyllium Husk, Sodium bicarbonate and Micro crystalline cellulose procured from Merck Specialities Pvt Ltd, Mumbai, India. Citric acid procured from Laser Chemicals, Ahmedabad, India. Magnesium Stearate procured from Apex Chemicals, Ahmedabad, India. Talc procured from S.D. Fine Chem., Mumbai, India.

Characterization of Sotalol:

Organoleptic properties:¹⁴

Take a small quantity of sample and spread it on the white paper and examine it visually for color, odour and texture.

Determination of Sotalol Melting point:

The melting point of Sotalol was determined by capillary tube method according to the USP. A sufficient quantity of Sotalol powder was introduced into the capillary tube to give a compact column of 4-6 mm in height. The tube was introduced in electrical melting point apparatus and the temperature was raised. The melting point was recorded, which is the temperature at which the last solid particle of Sotalol in the tube passed into liquid phase.

Determination of Sotalol Solubility:

Determination of solubility of drug by visual observation. An excess quantity of Sotalol was taken separately and adds in 10 ml of different solutions. These solutions were shaken well for few minutes. Then the solubility was observed and observations are shown in the Table.

Analytical method development:¹⁵

Preparation of 0.1N HCl:

Diluted 8.5mL of Concentrated Hydrochloric acid to 1000mL of Purified water and mixed

a) Determination of absorption maxima:

A solution containing the concentration 10µg/mL drug was prepared in 0.1N HCL UV spectrum was taken using Double beam UV/VIS spectrophotometer. The solution was scanned in the range of 200 – 400nm.

b) Preparation calibration curve:¹⁶

10mg Sotalol pure drug was dissolved in 10ml of methanol (stock solution1) from stock solution 1ml of solution was taken and made up with10ml of 0.1N HCL (100μg/ml). From this 1ml was taken and made up with 10 ml of 0.1N HCL (10μg/ml). The above solution was subsequently diluted with 0.1N HCL to obtain series of dilutions Containing 2, 4, 6, 8, 10µg/ml of per ml of solution. The absorbance of the above dilutions was measured at 230nm by using UV-Spectrophotometer taking 0.1N HCL as blank. Then a graph was plotted by taking Concentration on X-Axis and Absorbance on Y-Axis which gives a straight line Linearity of standard curve was assessed from the square of correlation coefficient (R²) which determined by least-square linear regression analysis.

Formulation development of floating Tablets:

Procedure for direct compression method:

1) Drug and all other ingredients were individually passed through sieve no ¹ 60.

2) All the ingredients were mixed thoroughly by triturating up to 15 min.

3) The powder mixture was lubricated with talc.

4) The tablets were prepared by using direct compression method by using 7mm punch.

FORMULATION OF TABLETS:

Table 1: Formulation composition for Floating tablets

INGREDIENTS (MG)	FORMULATION CODE
INGREDIENTS (MG)	F1	F2	F3	F4	F5	F6	F7	F8	F9
Sotalol	40	40	40	40	40	40	40	40	40
Sodium CMC	40	80	120	-	-	-	-	-	-
Chitosan	-	-	-	40	80	120	-	-	-
Psyllium Husk	-	-	-	-	-	-	40	80	120
Citric acid	10	10	10	10	10	10	10	10	10
Sodium bicarbonate	15	15	15	15	15	15	15	15	15
Micro crystalline cellulose	Q.S	Q.S	Q.S	Q.S	Q.S	Q.S	Q.S	Q.S	Q.S
Magnesium Stearate	4	4	4	4	4	4	4	4	4
Talc	5	5	5	5	5	5	5	5	5
Total Weight	250	250	250	250	250	250	250	250	250

RESULTS AND DISCUSSION:

Fig 1: Standard graph of Sotalol in 0.1N HCL

Preformulation parameters of powder blend:

Table 2: Pre-formulation parameters of blend

Formulation Code	Angle of Repose	Bulk density (gm/mL)	Tapped density (gm/mL)	Carr’s index (%)	Hausner’s Ratio
F1	30.45±0.43	0.312±0.12	0.354±0.01	11.86±0.04	1.134 ±0.13
F2	29.89±0.23	0.314±0.21	0.358±0.12	12.29±0.16	1.140±0.07
F3	30.25±0.26	0.315±0.13	0.362±0.12	12.98±0.09	1.149±0.02
F4	28.6±0.24	0.314±0.11	0.360±0.14	12.77±0.07	1.146±0.15
F5	29.45±0.34	0.318±0.12	0.366±0.13	13.11±0.11	1.150±0.06
F6	30.23±0.24	0.326±0.11	0.365±0.14	13.42±0.05	1.155±0.12
F7	26.82±0.34	0.449±0.13	0.530±0.11	15.28±0.14	1.180±0.04
F8	29.81±0.32	0.452±0.14	0.536±0.14	15.67±0.06	1.185±0.11
F9	30.42±0.36	0.453±0.11	0.538±0.11	15.79±0.17	1.187±0.03

Table 3: In vitro quality control parameters

Formulation codes	Weight variation (mg)	Hardness (kg/cm²)	Friability (%loss)	Thickness (mm)	Drug content (%)	Floating lag time (sec)	Total Floating Time(Hrs)
F1	249.50	5.6	0.31	3.64	99.61	53	5
F2	248.32	5.0	0.28	3.36	98.29	47	7
F3	245.20	5.4	0.25	3.66	99.87	63	8
F4	248.75	5.1	0.29	3.19	97.62	45	6
F5	246.86	5.9	0.24	3.54	99.46	36	8
F6	247.21	5.7	0.20	3.82	99.90	49	8
F7	249.36	5.3	0.37	3.91	98.67	51	5
F8	248.03	5.2	0.31	3.37	99.83	56	6
F9	247.89	5.8	0.25	3.49	98.41	49	8

Table 4: Dissolution data of Floating Tablets

Time (hrs)	F1	F2	F3	F4	F5	F6	F7	F8	F9
0	0	0	0	0	0	0	0	0	0
0.5	25.28	19.75	15.36	29.93	26.81	18.62	30.04	27.78	19.57
1	33.45	23.24	20.91	35.42	30.15	21.93	37.99	33.88	25.81
2	48.36	32.99	27.06	40.89	35.90	28.10	49.76	42.65	32.29
3	57.47	49.31	32.14	48.10	42.73	34.54	55.36	50.22	49.39
4	63.33	55.08	40.75	53.59	48.29	42.37	62.24	56.42	55.12
5	70.21	60.72	47.22	59.36	52.46	50.84	77.96	61.67	61.58
6	75.98	66.55	53.89	65.14	57.73	54.36	84.48	67.91	65.66
7	81.65	71.37	57.34	71.80	64.12	60.11	92.71	72.55	70.73
8	98.12	87.28	65.82	89.25	70.97	68.29	97.99	88.26	78.81
9		92.36	73.93	96.87	77.30	74.43		94.43	82.98
10		97.51	81.11		84.12	80.19		98.79	89.15
11			86.39		95.79	87.23			91.44
12			92.74		99.84	95.91			95.22

From the dissolution data it was evident that the formulations prepared with Sodium CMC as polymer were retarded the drug release 12 hours.

Whereas the formulations prepared with higher concentration of Chitosan retarded the drug release up to 12 hours in the concentration 120mg. In lower concentrations the polymer was unable to retard the drug release up to 12hrs.

Whereas the formulations prepared with Psyllium Husk were retarded the drug release in the concentration of 120mg (F9 Formulation) showed required release pattern i.e., retarded the drug release up to 12 hours and showed maximum of 95.22% in 12 hours with good retardation.

Hence from the above dissolution data it was concluded that F5 formulation was considered as optimised formulation because good drug release (99.84%) in 12 hours.

Application of Release Rate Kinetics to Dissolution Data for optimised formulation:

Fig 2: Higuchi release kinetics

Optimised formulation F5 was kept for release kinetic studies. From the above graphs it was evident that the formulation F5 was followed Higuchi release kinetics mechanism.

There was no disappearance of any characteristics peak in the FTIR spectrum of drug and the polymers used. This shows that there is no chemical interaction between the drug and the polymers used. The presence of peaks at the expected range confirms that the materials taken for the study are genuine and there were no possible interactions.

Sotalol are also present in the physical mixture, which indicates that there is no interaction between drug and the polymers, which confirms the stability of the drug.

CONCLUSION:

Hydrodynamically balanced tablets of Sotalol can be formulated with an approach to increase gastric residence and thereby improve drug bioavailability.

An attempt to develop floating tablets of Sotalol, using sodium bicarbonate as gas generating agents and Chitosan as polymer by direct compression technique was achieved.

The formulated tablets showed compliance for various physiochemical parameters viz. tablet dimensions, total floating time and drug content.

The dissolution studies formulations of F5 were good release and F5 formulation was excellent.

Data obtained from kinetic treatment revealed F5 formulations follow Higuchi release kinetics mechanism model.

The results of stability studies indicated that the most suitable storage temperature for Sotalol floating tablets was 40^oC/70%RH for a period of 90 days.

ACKNOWLEDGEMENT:

Thе Authors arе thankful to Principal, Department of Pharmacy, Samskruti College of Pharmacy, Hyderabad, for extending the support to carry out the research work. Finally, the authors express their gratitude to the Sura Labs, Dilsukhnagar, Hyderabad, for providing research equipment and facilities.

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Received on 08.10.2022 Modified on 07.11.2022

Asian J. Pharm. Tech. 2023; 13(1):41-46.

DOI: 10.52711/2231-5713.2023.00008