INTRODUCTION:

Tablets are a solid dosage form; it made in different sizes and shapes, and the drug substance may comprise 0.1% to 90% of a tablet bulk. From the ease of manufacture, tablet production, compared with other dosage forms, provides the highest output per manufacturing hour, and is the most economical, especially if one considers modern manufacturing methods involving processes such as the direct compression (DC) or fluidized-bed granulation (1). While tableting may appear from what has been said to be a simple process, it is often far from straightforward (2). Drug molecules show differences in physical and chemical properties. These include differences in their crystalline structure, particle size, water-solubility, dose, and sensitivity to hydrolysis or oxidation, topics discussed elsewhere in this book.

Hence, every drug molecule must treat as a unique entity for formulation. Drugs synthesized have been increasingly showing limited water solubility, reduced flow and compression properties, and sensitivity to moisture and heat (2). Potassium chloride extended tablet helps to cure hypokalemia; hypokalemia means potassium deficiency in the blood. In tablet Potassium chloride is an active ingredient, Hydrogenated vegetable, and Ethocel 100 FP oil is a release controlling agent, Ethocel 10 FP is a binder, Colloidal silicon dioxide, Talc, Syloid, and magnesium stearate is a glidant and lubricant, Isopropyl alcohol is a solvent, OpadryII85F520112 Yellow is a coating material (3). Seven formulations are carried out by wet granulation and direct compression method. For this seven stability study, also carry out to known quality.

AIM and OBJECTIVES:

To formulate and evaluate potassium chloride extended-release tablets

The study was carried out in the following stages:

· To Development and in vitro evaluation of potassium chloride extended-release tablets.

· To carry out pre-formulation studies.

· To carry out the stability studies of the formulated extended-release dosage form as per ICH guidelines.

MATERIALS AND METHODS:

Table No: 1 List of materials and their manufacturers or suppliers.

S. No	Materials	Functions	Manufacturers/suppliers
1.	Potassium chloride	Active Ingredient	Klinge Chemicals Limited
2.	Hydrogenated vegetable oil	Release controlling agent	Abitech corporation
3.	Ethocel 100 FP	Release controlling agent	Colorcon Asia Pvt lid
4.	Ethocel 10 FP	Binder	Colorcon asiapvt lid
5.	Colloidal silicon dioxide	Glidant	Cabot Sanmar lid
6.	Talc	Glidantand Lubricant	Luzenac
7.	Syloid	Glidant	Grace Davison
8.	Magnesium stearate	Lubricant	Valerusspeciality chemicals
9.	Isopropyl alcohol	Solvent	Merck
10.	OpadryII85F520112 Yellow	Coating material	Colorcon Asia Pvt lid

The tablet production active ingredients and binders should add for mixing into the rapid mix granulator and pass into sieving add glidant, lubricant pass into fluid bed equipment collect the product and send to tablet compression machine the reservoir coated by controlled release materials (Hydrogenated vegetable oil, Ethocel 100 FP). Finally, it reaches the taste masking and colour coating (4).

Reference Products details:

Label claim: Each tablet contains Potassium Chloride 750mg

Manufactured By: Upsher -Smith laboratories inc

Storage: Store at controlled room temperature, 15-30°C (59-86°F).

Excipients: Hydrogenated vegetable oil, magnesium stearate, polyethylene glycol, polyvinyl alcohol, silicon dioxide, talc and titanium dioxide. Yellow tablets also contain D&C Yellow No. 10 aluminium lake and FD&C Yellow No. 6 aluminium lake.

DISSOLUTION:

Instruments Required:

Dissolution Apparatus. and High-performance liquid chromatography With CAD (6).

Dissolution Conditions: Apparatus: Paddle, Medium: Milli- Q Water, Volume: 900mL, RPM: 50, Temperature: 37±0.50 C, Time points: 1, 2, 4, 6, 8, 12, 16and 150RPM

Preparation of 0.2 M Ammonium Acetate: (7) Weighed and transfer 15.4g of Ammonium Acetate into 1000 mL volumetric flask. Dissolve and dilute volume with water, adjust pH to 4.0 with acetic acid. Mobile Phase A: 100% Acetonitrile, Mobile Phase B: 100% Water, Mobile Phase C: 0.2M Ammonium Acetate Buffer.

Potassium Chloride Standard Preparation: (750 mg) (7) Weighed and transferred 42.0 of potassium chloride standard into 50mL flask, added 30ml dulcet and sonicated 5.0mins and diluted volume with diluents. Filtered through 0.45 filter.

Sample Preparation:

Using the dissolution apparatus and fill the washed bowls with 900ml each of dissolution media. Maintain the medium of the temperature of 37°C +/0.50 C. Place six tablets separately in six bowls and start the instrument. After the specified time, withdraw a required quantity of sample and run the dissolution apparatus before it fixes the paddle on the basket above 1cm of the basket. Filter the sample through 0.45m nylon membrane filter. Discard the first few ml of filtrate. Collect the filtrate, and use as a sample solution.

Procedure:(8)

Before starting the system equilibrate the column with gradient composition at least 2 hours. Inject gradient (1 injection), Blank (1 injection), 6 Standard preparation. The %RSD for area response of 6 replicate injection should be no more than 5.0%. Tailing factor for standard potassium peak should not be >2.0. If system suitability parameters pass, inject sample preparation one injection into the chromatograph. Record the chromatograms.

ASSAY: (BY HPLC) (6):

Instruments Required:

High-performance liquid chromatography with CAD.

Preparation of 0.2 M Ammonium Acetate:

Weighed and transfer 15.4g of Ammonium Acetate into a 1000ml volumetric flask. Dissolve and dilute volume with water, adjust PH to 4.0 with acetic acid.

Mobile Phase A: 100% Acetonitrile, Mobile Phase B: 100% Water, Mobile Phase C: 0.2 M Ammonium Acetate Buffer.

Potassium chloride Standard preparation: (7)

Weighed and transferred 42.0mg of potassium chloride standard into 50ml flask, added 30ml diluent, and sonicate 5.0mins and diluted volume with diluent. Filtered Through a 0.45 filter.

Sample preparation: (7)

Weighed 20 tablets and determined the average weight. Weigh and transferred the powdered tablets equivalent to 210mg into 250ml flask, add 150ml diluent, sonicate 40 mins with moderate shaking and kept 15 minutes for settling down and make up the volume with diluent, mixed well. Filtered through 0.45m filter and inject.

Procedure: (7)

Before starting the system equilibrate the column with gradient composition at least 2 hours. Inject gradient (1 injection), Blank (1 dose), 6 Standard preparation and check for system suitability parameters, The %RSD for area response of 6 replicate injection should be no more than 5.0%. Tailing factor for standard peak should not be more than 2.0. If system suitability parameters pass, inject sample preparation one dose into the chromatograph. Record the chromatograms.

DRUG PROFILE:

Details of Drugs (9):

Category: Electrolyte replenisher.

Description: white crystalline solid

Chemical Name: Potassium chloride

Chemical Formula: Cl K

Molecular Weight: 74.5513 g·mol⁻¹

Melting Point: 770 °C (1,420 °F; 1,040 K)

Boiling Point: 1,420 °C (2,590 °F; 1,690 K)

Refractive Index: 1.4902 (589 nm)

Solubility: soluble in glycerol, alkalies

RESULTS:

Blend parameters:

Table No:2 Blend parameters (10)

S. No	Number of Formulation	LOD	Bulk density (gms/ml)	Tap density (gms/ml)	Compressibility index %	Hausner’s ratio
1.	F1	---	0.781	0.937	16.59	1.198
2.	F2	---	0.810	0.967	16.31	1.193
3.	F3	1.33%	0.751	0.882	14.96	1.176
4.	F4	1.39%	0.732	0.833	12.16	1.137
5.	F5	1.56%	0.789	0.909	13.21	1.152
6.	F6	0.45%	0.750	0.857	12.50	1.142
7.	F7	0.06%	0.831	0.909	8.58	1.093

THICKNESS, HARDNESS, AND FRIABILTY VALUES:

COMPARATIVE DISSOLUTION PROFILE (% DRUG RELEASE) (10):

Table No: 3 Post compression parameters

Name of the tests	F1	F2	F3	F4	F5	F6	F7
Thickness (mm)	5.75	5.78	6.25	6.30	6.85	6.58	7.15
Hardness (Newton)	40N	70N	75N	68N	100N	70N	68N
Friability (%)	1.11%	0.99%	0.7%	0.19%	0.17%	0.15%	0.13%

FORMULATIONS DRUG RELEASE DATA:

Table No: 4 Dissolution data for F3, F4, F5, F6, F7

Time intervals (hrs)	Reference	F3	F4	F5	F6	F7
1	42.1	58.3	54.4	49.2	51.5	40.7
2	53.1	63.6	67.6	66.3	60.1	48.9
4	54.9	74.1	85.7	83.8	71.0	53.4
6	63.5	83.8	96.2	84.6	74.9	58.6
8	67.1	85.5	102.4	86.6	83.7	65.9
12	80.6	85.6	101.0	98.1	87.6	75.4

Formulation 3:

Figure No:1 Dissolution profile for referfence F3

F1 Value (Acceptance criteria 0-15) = 24.80, F2 Value (Acceptance criteria 50-100) = 40.07

Assay:

Table No: 5 Assay values of formulation trials

Formulation no:	mg/tab	% release
F3	750	99.7
F4	750	100.2
F5	750	101
F6	750	99.9
F7	750	100.3
F8	750	100.1

STABILITY DATA:

Description:

Assay: 100.1% (Initial), 100% (one month)

Dissolution at 2 hrs.: 48.9% (Initial), 49.5% (one month)

Water by KF: 0.42% (Initial), 0.43% (one month)

DISCUSSION:

F1 and F2: In the present study of the tablet was formulated by a direct compression method. In these trials, the blend parameters like bulk density, tapped density, compressibility index, and Hausner’s ratio showed poor flow property characteristics of the blend. it was reflected in the compression as the tablets showed weight variation. during the compression lamination it was observed at the hardness above 50N, weight variation observed, friability also more than the acceptance limit (1%). Hence next trial is planned to perform with non-aqueous granulation to check the process feasibility.

F3: This trial was formulated by a non-aqueous granulation method using binder HPC (hydroxyl propyl cellulose). Also, the blend parameters evaluated. During the compression at above 100-110N lamination was observed, friability and lamination tendency comparatively decreased than the previous batch, during the film coating uniform distribution of the film was not wholly attained. Dissolution is faster than reference; the Dissolution profile did not match with F1, F2 acceptance criteria. Hence it was suggested to increase the binder levels.

F4: The blend parameters evaluated. However, During the granulation in RMG some extent over wetting was observed, during drying large lumps are not broken, Tablets parameter like thickness, hardness, friability, was found to be satisfactory., friability problem significantly minimized, lamination observed during the hardness testing of the tablets at above 90N. and indicating the dissolution profile not match with F1, F2 acceptance criteria. Dissolution is faster than reference. Hence further trials were planned with Ethylcellulose to control the release.

F5 and F6: These trials were formulated by wet granulation method using ethyl cellulose 100cps 30mg/tab and 50mg/tab of respectively, Physical appearance of the tablets found to be satisfactory in both batches, Dissolution profile did not match with F1, F2 acceptance criteria. But the problem was significantly minimized, hence it was suggested to increase the level of the polymer.

F7: This trial formulated by wet granulation method used ethyl cellulose 100 cps in 70mg/tab. The blend parameters evaluated, Granules compressed at a hardness of 65-70Newtons. Tablets parameters were found to be satisfactory, indicating that drug release was similar to compared with the reference product. The dissolution profile of this trial was within the F1, F2 acceptance criteria.

CONCLUSION:

In the present study, Potassium chloride extended-release tablets were prepared using a nonaqueous granulation method. Ethylcellulose (Ethocel 100 FP) used as release controlling polymer, Ethylcellulose (Ethocel 10 FP) used as a binder. Different level of Ethylcellulose (Ethocel 100 FP) used in the development and F 7 experiment with Ethylcellulose (Ethocel 100 FP) 70mg/tab was considered to the optimum since dissolution profile is comparable with the reference product. F7 located for stability, up to one-month duration tablets were stable at 40°C ± 2°C 75% RH ± 5%, stability process still going on.

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Received on 18.10.2019 Modified on 27.12.2019

Research J. Pharm. and Tech. 2020; 13(10):4697-4701.

DOI: 10.5958/0974-360X.2020.00826.4