International journal of

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International Journal of
Chemical and Pharmaceutical Sciences
Formulation and Evaluation of oral controlled release matrix tablets of
Paroxetine
Mahendar R *, Sambashiva D, Valmiki R and Ramakrisha K MRR College of B. Pharmacy, Nadergul village, Saroornagar, Andhra Pradesh, India. *Corresponding Author: E-Mail: [email protected]
ABSTRACT
The purpose of the present study was to formulate and evaluate oral extended release matrix tablets of Paroxatine using hydroxy propyl methylcellulose (HPMC) and polyethylene oxide (PEO) as the release rate retardant polymers. The study includes in vitro characterization of tablets such as physico chemical properties, in vitro dissolution, DSC and FTIR. Selected formulations based on the in-vitro drug release study were packed in HDPE containers and kept for accelerated stability condition at 40°C and 75 % relative humidity. In vitro release studies revealed that the release rate decreased with increase in polymer concentration, polymer viscosity. In-vitro release kinetics indicated that the drug release from the matrix tablets was followed first order kinetics with diffusion mechanism. Results of Differential scanning calorimetry (DSC) and Fourier Transforms Infrared Radiation measurement (FT-IR) of initial and stability samples have shown that there was no incompatibility observed between the drug and excipients used in the formulation of matrix tablets. The developed controlled release matrix tablets of were stable up to three months. The release rate of the matrix tablets for prolonged periods of time can be advantageous than conventional Paroxatine tablets.
Key words: Paroxatine, matrix tablets, controlled release, stability, DSC, FTIR.
1. INTRODUCTION
hydrochloride upon oral administration, the Extended release is a kind of controlled development of controlled release delivery system release system that provides the medication for is required, that can maintain therapeutic drug most popular route of drug administration because of its ease of administration and patient as rate-controlling polymers for extended release compliance [2]. Even though oral route is preferred matrix-type dosage forms. Hydroxy propyl methyl by the patients, in case of chronic situations the cellulose (HPMC) is a hydrophilic polymer used in dosage form should be administered in divided the matrix type systems for the prolonged drug doses for longer periods of time and again this is a release. HPMC matrix tablets may be affected by non compliance to patients. There are several several formulation variables, such as polymer disadvantages if the drug is administered concentration [9] molecular weigh [10] drug levels frequently [3]. Dose modification is required in and solubility [11], type of excepient and tablet such situations [4]. Extended release (XR) shape and size [12]. The Hydrophilic polymer formulations are preferred because they offer matrix swells as water diffuses into the tablet. better patient compliance, maintain uniform drug Usually HPMC upon contact with aqueous media levels, reduce dose and side effects, and increase begin to hydrate, swell, coalesce, and form a viscous phase around the surface of the tablet. For hydrophilic matrix tablets comprised of water- phenylpiperidine antidepressant agent which soluble, swellable polymers such as HPMC, the selectively inhibits serotonin reuptake (SSRI) release kinetics are described by drug diffusion Paroxetine hydrochloride is heavily prescribed and polymer dissolution, i.e surface erosion. Drug drugs and effective in patients with various release is dependent on the relative contribution psychiatric disorders. However, there were of diffusion and erosion release mechanisms [13]. adverse effects associated with SSRI. Certain The matrix geometry is also one of the important adverse effects are thought to be linked to factors for drug releases from extended-release increased serotonin in the CNS (e.g. sexual dosage forms [14]. Specifically for HPMC matrix dysfunction and somnolence) and periphery tablets, the effect of matrix geometry on drug decrease these adverse effects of paroxetine release has also been studied in detail [15]. Poly
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(ethylene oxide) (PEO) is a hydrophilic polymeric
excipient that can be used in formulations for characterized for drug content. The lubricated different purposes [16]. PEO s are mostly used to granules were directly compressed on 16-station produce controlled release solid dosage forms tablet compression machine using 7 mm flat faced such as matrices, reservoirs, or coated cores. Due round (FFR) punch. (Cadmach Machinery Co, to their chemical structure, in the presence of Ahmedabad, India). Three batches were prepared water, control the release of the active moiety for each formulation and compressed in to tablets either by swelling or by eroding and swelling form each batch for the characterization study. forming a hydrogel. In both cases, the water 2.3. Characterization of the Designed Tablets
triggers the process starting the erosion and/or the swelling processes. PEO has been used in 2.3.1. Drug content estimation
association with HPMC to delay the release of a The drug content of the prepared matrix drug by controlling the extent and rate of swelling tablets was determined in triplicate. For each batch, 20 tablets were taken, weighed, and finely powdered. An accurately weighed 150 mg of this literature available on XR formulations of powder was taken and suitably dissolved under Paroxatine. The purpose of this study was to sonication (Power sonic 505, HWASHIN design oral XR tablet formulations of Paroxatine technology co) in pH 7.2 tris phosphate buffer and using HPMC and PEO as the retarding polymer. filtered through 0.45 µ (Millipore) filter. The The tablets were formulated by direct sample was analyzed after making appropriate compression method, and their physical and in vitro release characteristics were evaluated. The (Schimadzu, UV-1700 E 23) at 290 nm against effect of formulation factors such as polymer proportion, polymer type on the release 2.3.2. Hardness, weight variation and friability
characteristics was studied in order to optimize determination
The weight variation was determined by 2. MATERIALS AND METHODS
taking 20 tablets using an electronic balance (type Paroxatine was obtained as a gift sample ER182A, Mettler Toledo). Tablet hardness was from Alkem laboratories Ltd (Mumbai, India). determined for 10 tablets using a Monsanto tablet Hydroxypropyl methylcellulose (HPMC K 100 M) hardness tester (MHT-20, Campbell Electronics, were obtained from Colorcon Asia Private Ltd , Mumbai, India). Friability was determined by Poly (ethylene oxide) (Polyox WSR 303) was testing 10 tablets in a friability tester (FTA-20, obtained from The DOW Chemical Company, Campbell Electronics) for 300 revolutions at 25 Micro crystalline cellulose (Avicel PH 200) was obtained form FMC Biopolymers, USA, colloidal 2.3.3. In Vitro Drug Release Studies
silicon dioxide ( Aerosil ) was obtained form Degussa, Germany, talc was obtained form The in vitro dissolution studies were Luzenac, France and magnesium stearate was performed for the prepared tablets using obtained form Ferro Industrial Chemicals USA. All dissolution apparatus (LABINDIA, DISSO-2000, other chemicals and reagents used in the study Mumbai, India). The dissolution medium consisted of pH 7.2 tris phosphate buffer (900 mL), 150 rpm speed, maintained at 37 ±0.5 °C. The 2.1 Analytical method
samples were with drawn at different time method was used for the determination of spectrophotometer as per the method specified in Paroxatine using Schimadzu, UV-1700 E 23 in pH 7.2 tris phosphate buffer at 290 nm.
2.3.4. Fourier transforms infrared radiation
measurement (FT-IR)
2.2. Formulation of Paroxatine matrix tablets
The FT-IR spectra acquired were taken from dried samples. A FT-IR (Thermo Nicolet 670 spectrometer) was used for the analysis in the prepared using various proportions of HPMC and frequency range between 4000 and 400 cm-1, PEO as the retarding polymer. The tablets were with 4 cm-1 resolution. A quantity equivalent to 2 manufactured by the direct compression. The mg of pure drug and matrix tablets were selected drug, polymer(s) and all other excipients sifted through 425 μm sieve (ASTM mesh no 40) and mixed uniformly. The dry mix blend was mixed 2.3.5 Differential scanning calorimetry (DSC)
with aerosil and talc followed by magnesium
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Differential scanning calorimetry (DSC) study of matrix tablets was performed using a Diamond DSC (Mettler Star SW 8.10) to determine the drug excepient compatibility study. The analysis was performed at a rate 5 0 C min -1 from 500 OC to 2000 OC temperature range under Formulation
physical
characteristics of designed controlled release
matrix tablets of Paroxatine
Time (hrs)
Differential scanning calorimetry (DSC) study of pure Paroxatine showed a sharp endothermic peak at 132.5° C. The thermograms of Paroxatine matrix tablets showed similar endothermic peak at 132° C. This further confirms that there is no drug to polymer interaction. This was further conformed by FTIR
Figure -2: DSC thermogram of (A) pure
Paroxatine (B) Paroxatine matrix tablets
prepared with HPMC (C) Paroxatine matrix
tablets prepared with PEO .
3. RESULTS AND DISCUSSION
Prepared tablets were evaluated to weight variation study. The results of weight variation test are shown in the Table 1 and the values are around 120 mg. The tablets thickness of the prepared formulations was observed in the range of 3.5mm to 3.6 mm. The hardness of all the tablets was found to be in the range of 6 kg/cm2. The friability of the prepared tablets was below 1% clearly indicates the good mechanical strength of the tablets. The drug content ranged from 99.82 to 100.85 in formulation clearly indicating good content uniformity. The formulations were summarized in Table 1. The in vitro dissolution study showed that the drug release was extended Figure -3: FTIR Spectrum of (A) pure
up to 18 hours. The release for the formulations Paroxatine (B) Paroxatine matrix tablets
prepared with HPMC K 100 M was faster when prepared with HPMC (C) Paroxatine matrix
compared with the tablets prepared with tablets prepared with PEO .
Polyethylene oxide (PEO), The mainly depends up on the polymer type and the polymer concentration. The release kinetics form the dissolution data was followed zero order release with diffusion mechanism. Table 1 shows the release kinetics of the prepared paroxatine matrix tablets.
Figure -1: Cumulative percent drug release vs
time plot of Paroxatine tablets


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4. CONCLUSION
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ACKNOWLEDGEMENT
13. Ritger PL and Peppas NA. A Simple Equation Aurobindo Pharma for providing providing the for Description of Solute Release. II. Fickian gift samples of the drug and polymers.
and Anomalous Release from Swellable Devices, J. Contr. Rel., 1987; 6: 37–42.
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