Research Article

ISSN:2230-7346 Available online http://WWW.JGTPS.COM Journal of Global Trends in Pharmaceutical Sciences Vol.2, Issue 1, pp 43-54, January–March 2011

A.Arunachalam1, M.Karthikeyan2, S.AshutoshKumar2, S.Manidipa2, Kishore Konam3, Pottabathula hari Prasad4, S.Sethuraman*5, R.Senthilraj6 1. Department of Pharmaceutics, Sasikanthreddy College of Pharmacy, Nellore, A.P, India 2. Department of Pharmaceutics, AKRG College of Pharmacy, West Godavari, A.P, India. 3. Department of Pharmaceutical Analysis and QA, Sree Nagarjuna College of Pharmacy, Kadipikonda, Warangal, A.P, India. 4. Department of Industrial Pharmacy, Swami Ramananda Tritha Institute of Pharmaceutical Sciences, Nalgonda, A.P, India. 5. Department of Chemistry, SCSVMV University, Kanchipuram, Tamilnadu, India. 6. Department of Pharmaceutical Biotechnology, Vikas College of Pharmacy, Jangaon, Warangal, A.P, India. Corresponding author ABSTRACT Solid dispersions of a poorly water-soluble drug piroxicam in hydroxypropyl methylcellulose (HPMC) were prepared by spray drying technique. The physicochemical properties of the products and drug– polymer interactions were characterized by Scanning Electron Microscopy, Particle Size Analysis, and Fourier transform infrared spectroscopy, Determination of drug content etc. Piroxicam was found amorphously dispersed in solid dispersion systems with the drug to polymer weight ratio of 1:4.


usually poorly water-soluble increasing pharmaceutical formulation technologies are being developed to address this challenge of drug product development. solvent evaporation method circumvents the difficulties encountered with fusion method by working at milder conditions. Characterization.10 Fusion method. methylcellulose (HPMC).7–9 conventionally. excess usage of organic solvents and complication of product purity during the processing still hamper the application of solvent evaporation techniques. A number of water soluble polymers such as hydroxypropylcellulose. is precluded for many situations because of its high about processing temperature. INTRODUCTION: In order bioavailability drugs. Piroxicam. The conclusion sis a HPMC used to prepared effective pharmaceutical formulation of solid dispersion and to improve the bioavailability of poorly water-soluble drug. at which many active pharmaceutical ingredients. However. In-Vitro dissolution study. KEY WORDS: Solid Dispersion. Spray drying method. also called melt method.The techniques evaluated in this work resulted in improved dissolution of piroxicam. formation of complexes and solid dispersions2-4. HPMC. In solid dispersions drug molecules or very fine drug crystals are dispersed in a biocompatible or water-soluble matrix. and several been have commercialized in pharmaceutical market. solid dispersions are prepared by fusion method and solvent evaporation. The therapeutic usage of solid dispersions has been the focus of many recent studies. On the other hand. successful examples 5-6 1 1500C. an of to enhance number the of glycol (PEG) and Polyvinylpyrrolidone (PVP) have been used as carriers for solid dispersions. These include micronization. etc. hydroxypropyl polyethylene 44 .

nonflammable and available in large quantities. dispersion by supercritical fluids (SEDS). etc. gas antisolvent with (PCA).19 The spray drying processing can produce particles with controlled micrometric properties.Among many derivatives of solvent precipitation from gas-saturated solutions (PGSS). scCO2 is suitable to precipitate heat-sensitive drugs. and in some examples crystal habit. A variety of scCO2 techniques have been developed with different working principles. precipitation compressed (GAS). such as rapid expansion of supercritical solutions (RESS). Solid dispersions have been prepared using PCA processes. and most of the final products showed improved physicochemical and pharmaceutical properties. While further improvement is needed to make this technique sufficiently practical. PCA is of special interest because of its wide adaptability and mild operating condition. fluid supercritical antisolvent precipitation (SAS). alternative technologies are under development in pursuit of high product quality and low environmental impact. In the late 80’s. spray drying technique has been proven a powerful tool for preparing solid dispersions of drug and polymers11-12 because of its simplicity and effectiveness. supercritical fluids (SCF) started attracting interests in the pharmaceutical industry as an alternative to conventional processes. 20 evaporation method.060C) and low critical pressure (7. Owing to its mild critical temperature (31.13-14 The most common SCF is supercritical carbon dioxide (scCO2) which is nontoxic. which makes it more promising for pharmaceutical applications.15-18 These techniques were proven to effectively control particle size and reduce residual solvent content.17 Among numerous SCF techniques. precipitation antisolvent solution-enhanced the adverse effects of this technique on the crystalline and stability of pharmaceutical substances drive us to further exploit the potential of PCA processing of as a supplementary technology forming pharmaceutical solid dispersions. morphology and polymorphic form of the processed drug could be controlled as well.38 MPa). 45 .

with a co-axial nozzle with co-current flow. particle size analysis and determination of drug content etc. HPMC K100M. The total concentration of the solutions was 5 w/v%. pharmaceutical polymorphic characterization. (99. 1:2.Piroxicam Classification is a System with biopharmaceutical (BCS) class II well-defined various excipients were prepared using spray drying processing. and 1:4) in mixture of ethanol and acetone were fed into a mini-spray-dryer Bu¨ chi Mini Spray Dryer 290 (Flawil. Mumbai. Many studies have been conducted on its crystal form modification other and formulation with pharmaceutical- related materials.21 Its structure contains one O–H and one N–H group which can possibly form hydrogen bonds with the carbonyl group in the PVP repeat unit.7%) was supplied by GT&S.22–25 We prepared solid dispersions containing piroxicam and excipient (PVP K25) and their physicochemical properties were characterized by Fourier transform infrared spectroscopy (FTIR). The inlet temperature at the drying chamber was maintained around 110±20C and outlet temperature was 60±50C.. solid dispersions of pharmaceutical compounds in MATERIALS AND METHOD: MATERIALS: Piroxicam was purchased from Sun Pharmaceuticals Ltd.95%) Chennai and West and acetone dichloromethane from PA. 1:3.Ltd. chemicals and reagents were used without further purification. PA. Mumbai. Inc. the dissolution mechanisms of the solid dispersions were also discussed. Allentown. VWR All International. 46 . In addition. Chemicals PREPARATION OF SOLID DISPERSIONS OF PIROXICAM WITH HPMC K100M: Spray Drying Process: 26 Solutions of piroxicam and its mixtures with HPMC K100M (weight ratio=1:1. Chester. Switzerland) Pvt. In a recent study. Carbon dioxide (99. Ltd. Ethanol was purchased from Reachem Lab. and scanning electron microscopy (SEM). Loba Chemie Pvt.

model JEOL JSM-6701F. Samples were suspended in silicone oil Fourier Transform Infrared Spectroscopy (FTIR): Infrared spectra were collected on a Thermo Nicolet FT-IR spectrometer (Avatar 360. WI). A 10 mg sample was dissolved in 100 mL methanol. 47 . physical mixtures (PM) of piroxicam and HPMC K100M with weight ratio of 1:1.5 mLmin-1. measured using a laser diffraction size analyzer (LS 13 320. KBr pellets were Determination of Drug content: The content of piroxicam in the solid dispersion samples was determined using UV-Vis spectrophotometer (PERKIN ELMER). 1:3. Characterization of Formulated solid dispersion: 26-30 Scanning Electron Microscopy (SEM): A scanning electron microscope (SEM. Yields of 60% and higher amount were obtained. Dispersed samples were then fed into the analyzer. Madison. The samples Particle Size Analysis Particle size distribution was and treated by ultra sonication for 1 min. prepared and scanned over a range of 400– 4000 cm-1.Japan) was used to examine the particle size and morphology at 20 kV accelerating voltage. Fullerton. 1:2. Beckman. were fixed by mutual conductive adhesive tape on aluminum stubs and covered with a 250 A° film of gold–palladium using a sputter coater.The aspirator setting was 35 m3/h. and 1:4 were prepared by mixing the two components until a homogenous mixture was obtained. The spray feed rate was 5. CA). and then 1 mL of the stock solution was diluted to 50 mL with simulated gastric fluid (SGF) without pepsin. In addition. The spectra were obtained by averaging 32 scans at a resolution of 2 cm-1. Drug content was calculated from the absorbance measured at 334 nm. The spray-dried powders were prepared in duplicate.

2 and USP apparatus II (paddle) method. Bath temperature and paddle rotation speed were set at 37±0.2 mg piroxicam were added to 500 mL dissolution medium. Smaller the solid dispersion. The amount of drug dissolved was assayed spectrophotometrically at 334 nm at regular intervals. respectively.Japan) was carried out to study their morphological characteristics of Solid dispersions of piroxicam (ratio 1:4). faster will be the release rate of the drug from the solid dispersion. In each dissolution vessel.20C and 50 rpm. The particle size ranges of four formulations are as follows. Figure: 1 Figure: 2 equivalent of 10±0. Particle Size Analysis: Particle size determination was done by using a laser diffraction size analyzer. Size distribution plays an important role in determining the release characteristics of the solid dispersion. 48 . while larger the size. quantities of samples RESULTS AND DISCUSSION: Scanning Electron Microscopy (SEM): Scanning electron microscopy (JEOL JSM-6701F. NJ) using simulated gastric fluid (SGF) without pepsin at pH 1.In-vitro Dissolution Studies: The dissolution rate of piroxicam samples was measured in a Distek 2100C dissolution test system (Distek. North Brunswick. more sustained or controlled will be the release of the drug.

Also. F-III. The solid dispersion of formulations F-IV has highest mg of the drug content followed by the formulations F-I. the carbonyl group is more favorable in hydrogen bonding over the tertiary amine because of the steric hindrance of the latter group. 49 . a broad well defined band was observed in the Determination of drug content The drug content in the solid dispersion was determined by the procedure described earlier. revealing no perceptible interaction between the two 1 2 3 4 Formulations F-I F-II F-III F-IV Ratio (core: coat) 1:1 1:2 1:3 1:4 Particle size (µm) 39. The spectrum of physical mixture was simple summation of pure drug and HPMC K100M. respectively.76 42. F-II.47 The particle size is formulated batches of solid dispersion were found to be in the range of 39. Within each pyrrole ring of the HPMC polymer. Piroxicam contains one hydrogen donor (–OH and –NH) whose characteristic absorption bands are n O–H at 3339 cm-1 for form I and 3381 cm-1. Fourier Transform Infrared Spectroscopy (FTIR): FTIR is a very powerful technique in detecting presence of interaction in drug-carrier solid dispersions.34– 42. spectrum of HPMC K100M in 1600– 1700 cm-1 assigned to the carbonyl stretching vibration. The appearance or disappearance of peaks and/or the shift of their positions are often an indication of interactions such as hydrogen bonding.34 40.TABLE: 1 Particle size analysis of different batches of solid dispersion S.47 µm.52 41. The drug content of the different batches is as follows.

198 25.047 13.290 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 0.355 64.361 0.768 50.183 61.534 63.879 Formulations Ratio (core: coat) Drug content (mg) 1 2 3 4 F-I F-П F-III F-IV 1:1 1:2 1:3 1:4 58 63 71 78 IN-VITRO DISSOLUTION STUDY: The dissolution of solid dispersions of piroxicam and HPMC of products prepared by spray drying method.565 34.216 47.345 48.798 85.762 35.460 83.534 33.977 75.684 81.000 8. to enhance the dissolution of piroxicam more prominently.762 62.670 26.000 5.000 6.000 7. S.TABLE: 2 Drug Content of four different batches: S.762 0.564 24.796 73.286 16. Comparative dissolution study of different batches with various ratios of polymer Time in hours % of drug release F-I (Ratio 1:1) % of drug release F-II (Ratio 1:2) % of drug release F-III (Ratio 1:3) % of drug release F-IV(Ratio1:4) There are possible mechanisms responsible for dissolution of solid dispersions: drugcontrolled and carrier controlled dissolution.960 50 .321 36.756 27.546 49.753 80.204 14.235 87.649 15.

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