You are hereFORMULATION AND EVALUATION OF QUETIAPINE FUMARATE SUSTAINED RELEASE MATRIX TABLET

FORMULATION AND EVALUATION OF QUETIAPINE FUMARATE SUSTAINED RELEASE MATRIX TABLET


ABOUT AUTHORS:
Pranita T. Gaikwad*, Reshma R.Patil, Mr M.M.Nitalikar, Dr.S.S.Patil, Dr.S.K.Mohite
Rajarambapu college of pharmacy,
kasegaon-415404. MH
*pranitatgaikwad@gmail.com

ABSTRACT:
The main objective of the present work was to formulate sustained release matrix tablets of Quetiapine fumarate using different polymers viz. Hydroxy propyl methyl cellulose (HPMC) and Locust Bean Gum (LBG). Varying ratios of drug and polymer like were selected for the study. After fixing the ratio of drug and polymer for Sustain the release of drug up to desired time, the release rates were modulated by combination of two different rates controlling material and triple mixture of two different rate controlling material. After evaluation of physical properties of tablet, the in vitro release study was performed in 0.1 N HCl  pH 1.2 for 2 hrs and in phosphate buffer pH 6.8 up to 24 hrs. The effect of polymer concentration and polymer blend concentration were studied. Dissolution data was analyzed by Higuchi expression. It was observed that matrix tablets contained polymer blend of HPMC and LBG were successfully sustained the release of drug up to 24 hrs. Among all the formulations, formulation  P3 which contains 15 % HPMC K4M  and % 25 of LBG  release the drug which follow Higuchi kinetics via, diffusion and erosion and the release profile of formulation P3 was comparable with the prepared batch products. Stability studies (40±2ºC/75±5%RH) for 3 months indicated that Quetiapine fumarate was stable in the matrix tablets. The DSC and FTIR study revealed that there was no chemical interaction between drug and excipients.

REFERENCE ID: PHARMATUTOR-ART-2032

Introduction:
Quetiapine fumarate (QF) (bis [2-(2-[4-(dibenzo[ b,f][1,4]thiazepin-11-yl)]ethoxy)ethanol] fumarate, a dibenzothiazepine derivative, is a recent antipsychotic drug with an atypical neuropharmacological profile. Quetiapine is the antipsychotic that has the highest serotonin/dopamine binding ratio, being the serotonin type 2 (5-HT2)-receptor blocking effect about twice as strong as the dopamine D2-receptor blocking effect [1]. Due to this binding pattern, quetiapine causes minimal extrapyramidal side effects. It is readily absorbed from the gastrointestinal track with oral bioavailability of about 83% and a plasma elimination half life ranging from 6-7hours. Administration of QF in the sustain release dosage form as once daily would be more desirable as this formulation is intended to be given to schizophrenic patients. The sustain release form would also control the mood for longer period of time by maintaining the plasma concentration of drug well above the therapeutic concentration. It appears as effective as the older antipsychotics producing side effects no worse than those encountered with standard antipsychotics. This characteristic makes quetiapine well tolerated and effective in patients who are particularly susceptible to these severe side effects, including the elderly and adolescents and those with preexisting dopaminergic pathologies, such as Alzheimer’s disease and Parkinson’s disease.

An effort was therefore made to develop simple and effective sustain release tablets of Quetiapine fumarate using a polymer matrix system. Hydroxypropyl methyl cellulose (HPMC) is the most commonly and successfully used hydrophilic retarding agent for the preparation of oral sustain release drug delivery system [2]. The transport phenomena involved in the drug release from hydrophilic matrices are complex because the microstructure and macrostructure of HPMC exposed to water is strongly time dependent. Upon contact with the gastrointestinal fluid, HPMC swells, gels and finally dissolves slowly [3]. The gel becomes viscous acting as a protective barrier to both, the influx of water and the efflux of drug in solution [4, 5]. As reported by Ford et al, [6]the proportion of polymer in the formulation increases the gel formed is more likely to diminish the diffusion of the drug and delay the erosion of the matrix. Narasimhan and Peppas [7]. showed that the dissolution can be either disentanglement or diffusion controlled depending on the molecular weight and thickness of the diffusion boundary layer. The rate of polymer swelling and dissolution as well as the corresponding rate of the drug release are found to increase with use of lower viscosity grades of polymers. The rate of drug release form HPMC matrix is dependent on various factors such as type of polymers, drug, drug polymer ratio, particle size of drug and polymer, and the type and amount of fillers used in the formulation.

EXPERIMENTAL SECTION

Materials:

Sr. No.

Name Of Material Used

Use

Suppliers

1

Quetiapine fumarate (drug)


Active

ingredient

Lupin Research Park,Pune

2

HPMC K4M

Polymer

Colorcon Asia ,Goa

3

HPMC K15M

Polymer

Colorcon Asia ,Goa

4

HPMC K100M

Polymer

Colorcon Asia ,Goa

5

Locust Bean Gum

Polymer

SD fine lab chemicals

6

Lactose

Diluent

SD fine lab chemicals

7

Microcrystalline Cellulose(MCC)

Diluent

SD fine lab chemicals

8

Magnesium Stearate

Lubricant

SD fine lab chemicals

9

Talc

Glidant

SD fine lab chemicals

All other chemicals and reagents were of analytical grades.

PREPARATION OF MATRIX TABLET BY DIRECT COMPRESSION

METHOD:
Different tablet formulations were prepared bydirect compressionmethod .The formulations are composed of various concentrations of HPMC K4M and Locust Bean Gum in the ratios as drug and polymers  in various percentages. All powders were passed through 100- mesh sieve. The lactose and the polymer were mixed uniformly. Drug was added to the lactose and the polymer mixture and the blended for 20 min.  Blend  were then passed through sieve no.12 .The resulting mass were mixed with magnesium stearate and talc.  The lubricated mass  were compressed using 13mm die  punch (  KBr Press ) in to tablets. Compression pressure was adjusted during tabletting of each formula to get the tablet hardness in the range of 5 to 7 kg/cm3.The total weight of tablet was kept at 500 mg

Table no.1: Formulation table

Ingredients

P1

P2

P3

P4

P5

P6

P7

P8

P9

Drug(QF)

200

200

200

200

200

200

200

200

200

HPMC k-4M

  75

 75

 75

100

100

100

125

125

125

LBG

75

100

125

75

100

125

75

100

125

MCC

71

58.5

46

58.5

46

33.5

46

33.5

21

Lactose

71

58.5

46

58.5

46

33.5

46

33.5

21


Mg .stearate

4

  4

   4

   4

   4

  4

  4

  4

  4

Talc

   4

  4

  4

   4

  4

  4

   4

  4

  4

All ingredients are weigh in mg.

Evaluation of tablets
As mentioned in the preparation of tablet section, to study the effect of polymer concentration of drug release, 9 different formulas, having different concentrations of polymers HPMC and LBG were developed. Figure 1 shows the drug release profiles of the 9formulations studied.

The prepared tablets were tested as per standard procedure [17] for weight variation (n=20), hardness (n=6), thickness (n=6), drug content and friability. Hardness of the tablets was determined by using Monsanto tablet hardness tester, Friability test (n=10) was conducted using Roche friabilator (F. Hoffman-La Roche Ltd, Basel, Switzerland). Thickness of the tablets was measured by digital Vernier calipers (Aerospace). Drug content of QF was analyzed by measuring the absorbance of standard and samples at l=289 nm using the UV/Visible spectrophotometer (Schimatzu 1800) and comparing the content from a standard calibration curve.

Further the similarity factor f2 for the release of QF between the test product and that of the marketed formulation, Quel SR (IPCA Pharmaceuticals), was performed.

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