Formulation and Evaluation of Propanolol HCl Controlled Porosity Osmotically Controlled Tablet

R. Sakthikumar*, R. Lathaeswari, R. Senthamarai, T.N.K. Suriyaprakash and A. Anithaa

Department of Pharmaceutics, Periyar College of Pharmaceutical Sciences, K. Sathanoor Main Road, Tiruchirapalli-620021

ABSTRACT:

The objective of the present study is to formulate once daily controlled porosity osmotic tablet of Propanolol HCl for the treatment of Hypertension and to reduce the pill burden by avoiding dosing frequency. Controlled porosity osmotic tablets have an advantage of avoiding cost and labor. Six batches (F1-F6) of osmotic tablets were made with Mannitol, KCl and NaCl as osmotic agent by wet granulation technique. The granules were evaluated for precompression properties. The granules were compressed into tablet using Rotary tablet compression machine. The tablets were coated with Ethyl Cellulose (F1E-F6E) and Cellulose Acetate (F1C-F6C) as coating polymer i.e. semipermeable membrane. The tablets were subjected to evaluation parameters like weight variation, hardness, friability, % weight increase for coated tablet and in-vitro dissolution using USP Type I apparatus. All batches compiles with pharmacoepial standards. Among the twelve batches F5C showed sustained release over a period of 20 hrs with 80.59% drug release. The best formulation was subjected to stability studies for 3 months 45°C and 70% RH.

KEYWORDS: Propanolol HCl, Controlled porosity osmotic tablet, Ethyl Cellulose, Cellulose Acetate.

INTRODUCTION:

Propanolol is a β-adrenergic blocking agent used in the treatment of hypertension, Cardiac arrhythmias, Angina pectoris, Congestive Heart failure and in Myocardial infarction usually given in oral route. It has a half-life of 3-6 hrs. It will lead to increase the dosing frequency which in skip leads to adverse events. So, a controlled delivery system is essential to deliver the drug for a period of long time. Osmotic drug delivery systems are the most promising strategy for controlled drug delivery. They are the most reliable controlled drug delivery systems and could be employed as oral drug delivery systems¹. When these systems are exposed to water, low levels of water soluble additive is leached from polymeric material i.e. semi permeable membrane and drug releases in a controlled manner over a period of long time². It has the advantages like zero order release profile, independent of gastric pH³ and hydrodynamic condition, in-vitro and in-vivo correlation⁴. Controlled porosity osmotic tablets have an advantage of avoiding cost and labor. Mannitol, Kcl⁵ and Nacl⁶ were used as osmotic agents in the formulation. Drug release rate is directly proportional to the osmotic pressure of the osmogent used. Ethyl cellulose and Cellulose acetate⁷ were used as coating polymer i.e. semi permeable membrane that controls the drug delivery for a long period of time. PEG 400 was used as pore forming agent⁸. The objective of the present study is to formulate once daily controlled porosity osmotic tablet of Propanolol Hcl with various osmogents and coating polymer and to study the release characteristics.

MATERIALS AND METHODS:

Materials:

The drug Propanolol was obtained as gift sample from Madras Pharmaceuticals (Chennai). NaCl, KCl, Mannitol were purchased from sigma fine chemicals. HPMC K4M and PVP K 30(Kollidon) purchased from Caplican Pharma (Vellore). Ethyl Cellulose and Cellulose acetate were obtained from Loba chemie. All Chemicals used were of analytical grade.

Methods:

Formulation of the tablets:

Six batches were formulated with 40 mg of propanolol by wet granulation technique. The formula for the tablet was given in the Table-1. The drug and other excipients were triturated in the mortar and the granulating agent PVP dissolved in IPA was added to form a coherent mass. The Wet granules were passed through sieve no #10 and semidried. The semidried Granules were again passed through sieve no #22 and fully dried. Talc and Magnesium stearate were added to the dried granules. The Granules having good flow property was compressed in to tablet using 9 mm concave punch in 10 station Rotary tablet Compression machine. Weight of each tablet was 300 mg.

Table-1 Formula for Propanolol osmotic tablets

Ingredients	Weight (in mg)
Ingredients	F1	F2	F3	F4	F5	F6
Propanolol	40	40	40	40	40	40
Nacl	-	-	-	-	40	20
Kcl	-	-	40	20	-	-
Mannitol	40	20	-	-	-	-
HPMC K4M	15	15	15	15	15	15
PVP K30	15	15	15	15	15	15
Lactose	178	198	178	198	178	198
IPA	q.s	q.s	q.s	q.s	q.s	q.s
Magnesium stearate	6	6	6	6	6	6
Talc	6	6	6	6	6	6

Weight of the tablet = 300 mg

Formulations F1-F6 were coated as mentioned in the Table-2. It was passed through 200 mesh nylon cloth. The tablets were coated in the coating pan (Stainless steel) at a rotating speed of 32 rpm and spray rate at 4 ml/min. After coating, the coated tablets were dried at 50˚C for 12 hours to remove the residual solvent⁹.

Table-2 Formula for coating the tablets

Ingredients	F1E-F6E	F1C-F6C
Ethyl cellulose	5% w/v of acetone	-
Cellulose acetate	-	5% w/v of acetone
PEG 400	40% w/w of ethyl cellulose	40% w/w of cellulose acetate
Acetone	q.s	q.s

Evaluation of tablets:

The prepared tablets were evaluated for their weight variation by taking average of twenty tablets. The resistance of the tablet to chipping, abrasion or breakage under conditions of storage, transportation and handling before usage depends on its hardness. Hardness of tablets was determined using Pfizer hardness tester. Friability is a tablet property that evaluates the ability of the tablet to withstand abrasion in packaging, handling and shipping. Friability was measured by Roche Friabilator. % friability = (initial wt. – final wt. /initial wt.) * 100. The tablets that lose less than 1.0% of their weight are generally acceptable¹⁰. Twenty tablets (before and after coating) from each formulation were selected randomly, weighed individually and average weight was calculated. The average weight increase due to coating was determined from the difference in weight of coated and uncoated tablets. % Weight gain = (Weight gain/initial weight before coating) * 100

In-vitro drug release studies:

The coated tablets were subjected to in-vitro release study using Dissolution USP Type I apparatus at a temperature of 37± 5°C at a speed of 50 rpm. Release study was done in pH 1.2 buffer for first 2 hrs and then carried over in pH 6.8. 5 ml of samples were withdrawn at regular intervals and analyzed spectrophotometrically at 290 nm against blank.

Stability studies:

The best formulation F5C was subjected to stability studies for 3 months 45°C and 70% RH (ICH guideline Q3B). Samples were evaluated for content uniformity and in-vitro release after 30, 60 and 90 days.

RESULTS AND DISCUSSION:

The results for weight variation, hardness, friability and % weight increase for coated tablets were shown in the Table-3. Hardness ranges from 5-6 kg/cm². Friability is from 0.32 to 0.51%. All tablets were within the official limit (294 mg to 313 mg). % Weight increase for the coated tablets was between 5.46% and 6.12%.The results of dissolution studies were shown in the Figure-1 and 2. Among the 12 formulations F5Cshowed a release of 80.59% and F5E showed 85.21% for a period of 20 hrs. Formulation F5C containing Cellulose acetate showed a controlled release of drug when compared with F5E containing Ethyl cellulose.

Figure-1 Comparative dissolution profile for F1E- F6E:

Table-3 Evaluation parameters

Parameters	F1		F2		F3		F4		F5		F6
Parameters	F1E	F1C	F2E	F2C	F3E	F3C	F4E	F4C	F5E	F5C	F6E	F6C
Average Weight (mg)	298	294	308	297	312	299	305	312	302	305	305	296
Hardness (Kg/cm²)	5.2	5.6	5.8	5.3	6.1	6.5	5.8	5.4	5.8	5.6	5.8	5.6
Friability (%)	0.35	0.45	0.49	0.48	0.44	0.51	0.38	0.44	0.32	0.38	0.35	0.39
% Weight increase	5.88	5.96	5.64	5.72	5.98	5.96	5.80	5.82	6.12	6.10	6.04	6.02

Figure-2 Comparative dissolution profile for F1C-F6C

Stability studies showed that there was no significant change in drug content and in in-vitro release rate after 30, 60 and 90 days shown in Table-4. It indicates that the formulation F5Cwas stable, since it shows a sustained release over the other formulations.

Table-4 Accelerated stability data for F5C

Time in days	% Drug content	% cumulative drug release after 20 hrs
30	97.68	82.35
60	95.37	87.23
90	92.15	89.94

CONCLUSION:

It was concluded that Propanolol osmotic tablet prepared with Nacl as osmogent and Cellulose acetate as coating polymer has control the release of drug for 20 hrs, showing that release rate is directly proportional to the osmotic pressure of the osmotic agent, and thus decreasing the frequency of administration and thereby improving the patient compliance.

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