Optimization of Pellet Coating Techniques

 

Aparna Raut*1, PB Suruse3, JG Awari2, AK Raut2 and VV Kale3

1Dr. Reddys Labs. Ltd., Global Regualatory Affairts, Hyderabad, Andhra Pradesh -500 072  India.

2Department of Pharmaceutical Sciences, R. T. M. Nagpur University, Nagpur.

3Sharad Pawar College of Pharmacy, Wanadongri, Nagpur-441110.

 

ABSTRACT

In the present study, pellets were prepared and optimization of pellets coating technique was done. Extrusion-spheronization technique was employed to prepare pellets by optimizing operational variables like spheronization time, spheronization speed and percent of granulating fluid to obtain smooth and spherical pellets. Pellets were coated employing spray coating and powder layered coating techniques in order to obtain sustained release. Hydroxy Propyl Methyl Cellulose (HPMC) K-15M was used as a coating polymer. Diclofenac sodium loaded pellets (20%) were prepared with 76% MCC and PVP K-30 at spheronization speed of 120 RPM for 20 min using 76% granulating fluid. Spray coating was done employing HPMC K-15M solution (1%) in (70: 30) water: ethanol mixture. Powder layering was done using 5% PVP K-30 in (50: 50) ethanol: water mixture as binder solution and powdered HPMC K-15M. Both the processes were continued till 5% coating level was achieved. Powder layered and spray coated pellets were evaluated for physical characteristics like drug content and in-vitro drug release. Physical characteristics like angle of repose, bulk density, tapped density, friability, moisture content and percentage drug content were found to be within standard limits. In-vitro drug release was found to be 0.5 to 1% in pH 1.2 buffer from both the pellets. In pH 6.8 buffer powder layered pellets showed 25% drug release, while spray coated pellets showed 45% drug release after 7 h. From the above study, it was concluded that powder layered pellets sustain drug release more than spray coated pellets.

 

KEYWORDS: Pellets, Diclofenac sodium, Spray coating, Powdered layer coating, Extrusion-spheronization technique.

 

INTRODUCTION

Optimization is usually associated with minor modifications in the basic formula. The selection of a specific formulation depends on the coating equipment and conditions available, the intended purpose of coating and the total solid load desired in the coating (James et al., 1987). Diclofenac sodium, the sodium salt of [2-(2, 6-dichlorophenyl amino) phenyl] acetic acid, is a well known drug available in various pharmaceutical dosage forms. It is a potent nonsteroidal anti-inflammatory drug with pronounced analgesic and antipyretic properties (Oddsson et al., 1990). It has weak acidic properties (pKa about 4) and its solubility depends on the pH of the medium. It is slightly soluble in water, very slightly soluble in phosphate buffer at pH 6.8 and practically insoluble in hydrochloric acid at pH 1.1 (Adeyeye et al., 1990). Pelletization is an aglomeration process that converts fine powder or granules of bulk drugs and excipients into small, free flowing, spherical or spherical units referred to as pellets (Reynolds and Conine et al., 1970). Generally the particle sizes of pellets are between 0.5 to 1.5 mm depending on the preparation of technique (Ghebre et al., 1989). Pellets provide a reduction in the dosage regimen and gastrointestinal irritation moreover controlling the drug release and increasing the absorption of the active ingredient. Also one of the advantageous properties of the pellet formulations is being good candidates for the delivery of the drug substances due to minimizing the dose dumping effect (Palsson et al., 1990).


Figure 1: Calibration curve for Diclofenac sodium

 

Figure 2: Cumulative % Drug release from 5% powder layered pellets

 

Figure 3: Cumulative % Drug release from 5% spray coated pellets

 

The reproducibility of the release characteristics (Wu et al., 1998) from pellet formulations is also much better with respect to the single unit dosage forms (Zhon et al., 2003). They are suitable systems for film coating with respect to the low surface area-volume ratios (Iyer et al., 1993). Also, resistance to external factors such as moisture, air and light are the most advantageous properties of this dosage form (Heng). The objective of present study was to prepare pellets employing extrusion-spheronization technique (Dougles and Connor et al., 1989) and to optimize pellet coating techniques and to compare drug release from spray coated and powder layered pellets (Heng et al., 2001).

 

Figure 4: IR spectra of Diclofenac sodium

 

Figure 5: IR spectra of HPMC K-15 M

 

Figure 6: IR spectra of PVP K-30

 

MATERIALS AND METHODS:

Materials:

The active substance Diclofenac sodium is generously obtained from Zim Labs. Nagpur. Microcrystalline cellulose was purchased from Chemfield Ltd., HPMC K-15M from Colorcon Asia Pvt. Ltd., and PVP and PVP K-30 from Signet Chem.  All the reagents used in this research were of standard pharmaceutical grade.

Table 1: Preparation of Diclofenac sodium (20%) loaded pellets

Ingredient

Quantity (%)

Diclofenac sodium

20

MCC

76

PVP

4

Water

As required

 

Table 2: Processing conditions used to prepare Diclofenac sodium pellets

Spheronization time

20 min

Spheronization speed

120 RPM

% granulating fluid

76%

 

Table 3: Evaluation of physical parameters of pellets

Sr. no.

Property

Powder layered pellets

Spray coated pellets

1

Angle of repose

22.32

24.56

2

Bulk density

0.8

0.84

3

Tapped density

0.85

0.89

4

% friability

0.22

0.28

5

Mean diameter(µm)

1084

1032

6

Surface area (µm)

3689675.8

3344175.4

7

% Moisture content

2.42

2.98

8

% Drug content

99.24

99.10

 

Preparation of non-drug loaded pellets:

Microcrystalline cellulose (96%) was weighed and granulated with 4% PVP solution in water and additional water was added as needed to achieve consistency of the wet mass for extrusion-spheronization. The wet mass was immediately passed through extruder and extrudes so obtained was spheronized in the spheronizer (Umprayan et al. 1999). Various batches of above formulation were prepared keeping ingredients and their quantity constant and varying one processing variable at a time and keeping others constant.

 

Preparation of drug loaded pellets:

From the optimization of processing parameters like spheronization time, spheronization speed and % of granulating fluid using non-drug loaded pellets, Diclofenac sodium (20%) loaded pellets were prepared. Microcrystalline cellulose (76%) and Diclofenac sodium (20%) were weighed and granulated with 4% PVP solution in water. Additional water was added as needed to achieve consistency of the wet mass for extrusion-spheronization (Dyer et al., 1995). The wet mass was immediately passed through extruder and extrudes so obtained was spheronized in the spheronizer (Table 1).

 

Coating of drug loaded pellets:

Spray coating:

HPMC K-15M solution in water: ethanol (70: 30) mixture was used as coating solution. Preweighed quantity of Diclofenac sodium pellets were placed in a conventional coating pan and coating was continued till 5% coating obtained (Heng et al., 1996).

 

Powder layering:

5% binder solution of PVP K-30 was made in ethanol: water mixture. Weighed quantity of pellets was placed in a spheronizer at speed of 120 RPM. With the help of syringe drop by drop binder solution was added on rotating pellets in spheronizer followed by addition of powdered HPMC K-15M and the process was continued till 5% coating level was achieved (Oshlack et al.,).

Figure 7: IR spectra of pellet

 

Figure 8: IR spectra of MCC

 

Evaluation of pellets:

Characterization of pellets:

Pellets were characterized for parameters like friability (Sinha et al., 2005), angle of repose (Bankere et al., 1991), size distribution, bulk density, tapped density, moisture content, particle size and surface area (Martin et al., 1991). Particle size analysis and surface area determination was carried out by Motic Microscopy and results are shown in Table 3.

 

Construction of calibration curve for Diclofenac sodium:

A series of Diclofenac sodium concentration ranging from 5-50 µg/ml was made from

standard solution in pH 6.8 phosphate buffer. Absorbance was measured at 276 nm and

standard curve was made by plotting absorbance versus concentration of the drug.

 

Determination of drug content:

Crushed sample from each formulation equivalent to 100 mg drug was weighed and transferred to 100 ml volumetric flask and diluted to 100 ml with phosphate buffer and filtered. 1 ml solution was taken and diluted to 100 ml with pH 6.8 phosphate buffer and absorbance was measured at 276 nm and by using calibration curve of Diclofenac sodium drug content was determined.

 

In-vitro drug release:

In-vitro dissolution of drug loaded spray coated and powder layered pellets was carried out using USP Dissolution Apparatus 1(basket type). The dissolution test was performed using 900 ml of dissolution medium at 37± 0.5°C at 50 RPM. Dissolution medium used was pH 1.2 buffer for first 2 h and pH 6.8 buffer for next 5 h. Absorbance of these solutions was measured at 276 nm (Woodruff et al., 1972).

 

Stability studies:

Stability studies of pellets were carried out at 75% RH at 40°C for 45 days. Interaction of drug and excipients was studied by using UV and IR spectroscopy (Heng et al., 2000).

 

RESULT AND DISCUSSION:

From optimization of processing variables for shape of pellets, it was observed that spherical pellets were formed from the base formula for non drug loaded pellets at spheronization speed of 1000 RPM, spheronization time of 15 minutes and 96% of granulating fluid. The processing conditions used to prepare Diclofenac sodium pellets and the results of evaluation for physical parameters of both spray coated and powder layered pellets are shown in Table 1 and Table 2 respectively. Calibration curve for Diclofenac sodium are drawn by using pH 6.8 phosphate buffer at 276 nm (Figure 1). In vitro dissolution of pellets showed that powder layered pellets release 35% of drug in pH 6.8 buffer and spray coated pellets release 45% of drug in pH 6.8 buffer (Figure 2 and Figure 3). Stability studies revealed that the formulation developed was found to be stable under short-term stability studies. UV and IR spectroscopy showed no chemical interaction between drug and excipients.

 

CONCLUSION:

Both the formulation spray coated and powder layered pellet were evaluated for physical properties like angle of repose, bulk and tapped density, % friability, mean diameter (µm), surface area (µm), %moisture content and % drug content. From the evaluation of both coated pellets formulation posses good physical properties within specified ranges. The dissolution of optimized formulation batch was carried out in type-1 USP dissolution apparatus. The dissolution was carried out in pH 1.2 buffer for first 2 h and continued in pH 6.8 buffer. The results revealed that 5% spray coated pellet release 45% drug after 7 h in   pH 6.8 buffer while 5% powder layered pellet release only 35% drug. Thus, it can be concluded that powder layered pellets sustain drug release more than spray coated pellets. Stability study for the optimized formulation batch was performed for 45 days at 75% RH at 40°C. The drug content was determined by assay method. There was no significant change in the drug content when analyzed significantly. Thus stability study revealed that the combination formulation developed found to be stable under short term stability studies.

 

ACKNOWLEDGEMENT:

Authors are thankful to the HOD, Department of Pharmaceutical Sciences, RTM Nagpur University, Nagpur for his encouragement and extended support during entire course of research work.

 

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Received on 16.04.2009

Accepted on 12.06.2009     

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Research Journal of Pharmaceutical Dosage Forms and Technology. 1(3): Nov. – Dec. 2009, 184-187