DESIGN DEVELOPMENT AND IN VITRO EVALUATION CONTROLLED RELEASE TABLETS

DESIGN DEVELOPMENT AND IN-VITRO EVALUATION

CONTROLLED RELEASE TABLETS

Divya Sahu*, Dr. Arun Patel, Prof. Shailendra Patel and Prof. Neelesh Dwivedi

Department of Pharmaceutics, Shri Ram Group of Institutions Jabalpur (M.P.).

ABSTRACT

The present investigation was aimed at designing controlled release

matrix tablets of isradipine, (C19H21N3O5) using various natural

polymers like guar gum, karaya gum, xanthan gum and veegum,

individually and in combinations of various concentrations, to produce

controlled release of isradipine in order to improve the efficacy and

patient compliance and to compare the drug release profiles of

optimized formulation and commercial formulation by similarity and

difference factors. The drug release from the formulation was found to

be zero order. Using Higuchi's model and the Korsmeyer equation, the

drug release mechanism from the controlled release tablets was found

to be Anomalous (non-Fickian) diffusion. The values of difference factor, f1 and similarity

factor, f2 was found to be 1.74 and 63.38 indicating similarity between drug release profiles

of optimized formulation and reference product.

KEYWORDS: Buccal delivery, Isradipine, Mucoadhesion, First pass metabolism, Permeation Enhancers.

1. INTRODUCTION

For many decades treatment of an acute disease or a chronic illness has been mostly

accomplished by delivery of drugs to patients using various pharmaceutical dosage forms,

including tablets, capsules, pills, suppositories, creams, ointments, liquids, aerosols and

injectables as drug carriers. High patient compliance and flexibility in developing dosage

forms made the oral drug delivery systems the most convenient mode of drug administration

compared to other dosage forms. 1.

Volume 8, Issue 13, 1057-1062. Research Article ISSN 2277– 7105

*Corresponding Author

Divya Sahu

Department of

Pharmaceutics, Shri Ram

Group of Institutions

Jabalpur (M.P.).

Article Received on 13 Oct. 2019,

Revised on 03 Nov. 2019, Accepted on 24 Nov. 2019

2. FORMULATION OF ISRADIPINE TABLET

There are various methods for preparing matrix tablets, namely Direct compression, Wet

granulation, Melt granulation, Response surface methodology etc.

2.1. Wet Granulation

Required quantities of drug and polymer were mixed thoroughly, and a sufficient volume of

granulating agent is added slowly. After enough cohesiveness was obtained, the mass is

sieved through 22/44 mesh.

2.2 Direct Compression

Direct compression is regarded as a relatively quick process where the powdered materials

are compressed directly without changing the physical and chemical properties of the drug.

3. MATRIX DEVICES

One of the least complicated approaches to the manufacture of sustained release dosage

forms involves the direct compression of the blends of drug, retardant material and additives

to form a tablet in which the drug is embedded in a matrix core of the retardant.

Figure 6: Schematic Diagram of Matrix Systems.

In this model, drug in outside layer exposed to the bathing solution is dissolved first and

diffused out of the matrix. This process continues with the interface between bathing solution

and the solid drug moving controls, the rate of dissolution of drug particles within the matrix

must be faster that the diffusion rate of dissolved drug leaving matrix.

4. Preformulation Studies

Preformulation study may be described as a phase of the research and development process

where the formulation scientist characterizes the physical, chemical and mechanical

properties of new drug substances, in order to develop stable, safe and effective dosage

www.ajptr.com evaluation, possible interaction with various inert ingredients intended for

use in final dosage form was also considered.

Drug-Excipients Compatability Study by FT-IR Spectroscopy

FT-IR Spectroscopy of pure drug (Isradipine) and its formulations were carried out on Bruker

FTIR16000 model to investigate any possible interaction between the drug and the utilized

polymers (PEG 4000, PVP K30, Lycoat RS720). The samples were finely grounded with

KBr to prepare the pellets under a hydraulic pressure of 600 psi and a spectrum was scanned

in the wavelength range of 400 and 4000 cm-1 using Bruker FT‐IR spectrophotometer. The

compatibility of drug in the formulation was confirmed by comparing FTIR spectra of pure

drug with FTIR of its formulation.

CONSTRUCTION OF CALIBRATION Preparation of Standard Stock Solution

10 mg of Isradipine was accurately weighed and dissolved in 100ml volumetric flask

containing phosphate buffer of pH 6.8 and subjected to sonication. The volume is made up to

100ml with pH 6.8 phosphate buffer to produce a concentration of 100μg/ml, which is a stock

solution.

Determination of λmax Above solution was scanned between the range of 200-400nm by

Shimadzu 1700 model UV spectrophotometer. From the scan it was concluded that the λmax

of Isradipine was 285nm.

Calibration curve of Isradipine in phosphate buffer of pH 6.8.

From the standard stock solution aliquots 1ml, 2ml, 3ml, 4ml and 5ml were pipette out into

concentration of 10, 20, 30, 40 and 50μg/ml respectively. The absorbance of each

concentration was measured at λmax 285nm using UV Visible spectrophotometer against

blank (phosphate buffer of pH 6.8).

Melting method (fusion method)

Solid dispersion of Isradipine in PEG4000 or polyvinyl pyrollidone (PVP K30) containing

three different ratios (1:1, 1:1∙5 and 1:2 w/w) as seen in Table(1) were prepared by fusion

method. Required amount of drug and polymer were mixed in china dish, the mixture was

then heated using water bath at 70°C till it was completely melted.

Disintegration time

The disintegration time was measured using modified disintegration method. For this purpose

a petri dish was filled with 10 ml of water. The film was carefully put in the centre of petri

dish. The time for the film to completely disintegrate in to fine particles was noted in Table

3.26.

7. RESULTS AND DISCUSSIONS Particle Size

The Particle size was determined using mechanical sieve shaker as per the procedure. since

95% of the drug is retained on sieve # 50, the particle size of the drug lies between #50 and

#18 i.e. 300 um an 1.00 mm. The results are shown in the table 16.

Table 1: Particle Size Anlysis.

Sieve No Microns Wt of drug + sieve (g)

Wt of the drug retained (g)

% of drug retained

Cumulative % of drug retained (µ)

#18 1000 381.4 0.4 1.9 1.9

# 50 297 374 20 95.24 97.14

#70 210 335.6 0.6 2.86 100

#120 125 329 0 0 0

#140 105 323 0 0 0

#170 88 321 0 0 0

#200 74 322 0 0 0

#200 pass 502 0 0 0

21 100

Solubility

The solubility of Paroxetine Hcl was carried out in different buffers as per the procedure and

Table 2: Solubility of Paroxitine Hcl in Different Ph Conditions. Buffers Solubility(mg/ml)

1.2 1.93

4.5 6.31

6.8 1.39

7.4 1.23

DM water 3.13

Solubility of Paroxitine Hcl in different pH conditions

7. SUMMARY AND CONCLUSION

The present study was under taken to formulate and evaluate the controlled release tablets of

Paroxetine hydrochloride by using direct compression. The study involved preformulation of

drug and excipients, formulation, evaluation and stability studies.

Matrix tablets of Paroxetine hydrochloride (F1-F6) were prepared by using hydrophilic and

hydrophobic polymers like HPMCK4M, HPMCK100M and Ethyl Cellulose. Formulation F5

with polymeric combination of HPMC and ethyl cellulose showed a better drug release at the

end of 6th hr.

CONCLUSION

It may be concluded from the present study that slow, controlled release of Paroxetine over a

period of 6 h was obtained from matrix tablets. It is evident from the results that Hydrophilic

matrix of HPMC could not control the Paroxetine release effectively where as a combination

of hydrophilic and hydrophobic matrix prepared by HPMCK4M and ethyl cellulose is a

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