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Formulation and evaluation of microspheres with aceclofenac

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Aceclofenac is an analgesic and anti-inflammatory drug that reduces fever, pain, and inflammation in rheumatoid
arthritis, osteoarthritis and ankylosing spondylitis. Aceclofenac has higher anti-inflammatory action than
conventional NSAIDs. Development of microspheres is a promising technology for controlled release and drug
targeting. Various types of microspheres such as bio-adhesive, magnetic, floating, radioactive and polymeric
microspheres are developed for various purposes. Microspheres occupied a central place in novel drug delivery, it
can targeted and localized drug delivery system. This Aceclofenac Microsphere is Prepared by using Spray drying
Technique in which release rate of drug is mainly depends on formulation composition (Eudragit RS 30 D and
Ethyl Cellulose (1:2 ratio)). Formulated microspheres were characterized for particle size, encapsulation efficiency
and In vitro studies. The optimum drug-to-polymer ratio and feed flow rate is responsible for higher percent yield,
smaller particle size and maximum encapsulation efficiency.

Publié dans : Santé & Médecine
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Formulation and evaluation of microspheres with aceclofenac

  1. 1. www.wjpmr.com Savale. World Journal of Pharmaceutical and Medical Research 181 FORMULATION AND EVALUATION OF MICROSPHERES WITH ACECLOFENAC Sagar Kishor Savale1* *1 Department of Pharmaceutics, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur 425405, Dist. Dhule Maharashtra State, India. Article Received on 04/06/2016 Article Revised on 25/06/2016 Article Accepted on 15/07/2016 INTRODUCTION[1, 2, 3, 4, 5, 6, 7, 8] Microspheres have played a vital role in the development of controlled/sustained release drug delivery systems. Microspheres have been of particular interest from the pharmaceutical point of view providing the possibility to achieve sustained and controlled drug release. Microspheres are matrix systems that contains drug throughout their structure and are potential candidates for oral controlled release. Microsphere can be defined as solid spherical particles ranging from one to 1000 μm in size. The microspheres are free flowing powders consisting of proteins or synthetic polymers, which are biodegradable in nature. Microsphere is prepared by various techniques in which Aceclofenac Microsphere is prepared by using Spray drying technique. Spray drying is defined has the solidification is done by rapid evaporation coatings solution contain in coating polymeric material. Aceclofenac is a Non-Steroidal Anti- inflammatory drug (NSAIDS). Aceclofenac is important to show the Analgesic as well as anti-inflammatory activity for the prevention of Inflammation. The Basic mechanism action of drug to inhibit the COX I, COX II, (Cyclooxygenase I and Cyclooxygenase II) is Responsible for the Inflammation. The chemically Aceclofenac is known as 2-[[2-[2-[(2, 6-dichlorophenyl) amino] phenyl] acetyl] oxy] acetic acid. It is important to give symptomatic treatment of rheumatoid arthritis, osteoarthritis and ankylosingspondylitis. Aceclofenac is a drug is important to prevent the problem associated in gastric irritation and maintain the stability of GI environment. Aceclofenac is a drug is mainly used for the treatment of mild, moderate, postoperative pain and it is effective against menstrual pain and endometriosis. MATERIAL AND METHOD Material Aceclofenac and all Formulation Excipient (Eudragit RS 30 D, Ethyl cellulose, Iso Propyl Alcohol) was obtained from Pharmaceutics Laboratory of R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur 425405, Maharashtra State, one of the NBA and NAAC accredited and AICTE Approved institutes in India. Method The parameters of Authentication and Preformulation is carried out by pure drug Aceclofenac for Maintaining their Quality, Purity and Standard. AUTHENTICATION PARAMETERS[9,10,11,12,13,14,15] Melting Point Method Melting Point determination is one of the preformulation property in which the temperature at which it changes state from solid to liquid at atmospheric pressure. At the melting process the solid and liquid can exist equilibrium. The Melting point of Aceclofenac pure wjpmr, 2016,2(4), 181-187 SJIF Impact Factor: 3.535 Research Article ISSN 2455-3301 WJPMR WORLD JOURNAL OF PHARMACEUTICAL AND MEDICAL RESEARCH www.wjpmr.com *Corresponding Author: Sagar Kishor Savale Department of Pharmaceutics, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur 425405, Dist. Dhule Maharashtra State, India. ABSTRACT Aceclofenac is an analgesic and anti-inflammatory drug that reduces fever, pain, and inflammation in rheumatoid arthritis, osteoarthritis and ankylosing spondylitis. Aceclofenac has higher anti-inflammatory action than conventional NSAIDs. Development of microspheres is a promising technology for controlled release and drug targeting. Various types of microspheres such as bio-adhesive, magnetic, floating, radioactive and polymeric microspheres are developed for various purposes. Microspheres occupied a central place in novel drug delivery, it can targeted and localized drug delivery system. This Aceclofenac Microsphere is Prepared by using Spray drying Technique in which release rate of drug is mainly depends on formulation composition (Eudragit RS 30 D and Ethyl Cellulose (1:2 ratio)). Formulated microspheres were characterized for particle size, encapsulation efficiency and In vitro studies. The optimum drug-to-polymer ratio and feed flow rate is responsible for higher percent yield, smaller particle size and maximum encapsulation efficiency. KEY WORDS: Microspheres, Spray drying, Aceclofenac, Particle size, Encapsulation Efficiency.
  2. 2. www.wjpmr.com Savale. World Journal of Pharmaceutical and Medical Research 182 drug is determine by using two types of method one is Conventional method and another is Digital method. Log P Value Log p value is determined by using Partition Coefficient Phenomenon. In which The 1 gm of drug is added in separating funnel containing equal portion of 25 ml of Octanol and 25 ml of Water. The separating funnel is shake 20 – 25 min. and stabilized the mixture. After stabilizing the mixture to remove water phase from separating funnel and filter it. Take Absorbance of Filtrate and calculate the log p value. Solubility Studies The Term Solubility is defined as maximum amount of solute that can be dissolved in a given amount of solvent to form a homogenous system at specified temperature and Specific Pressure to from Saturated Solution. Procedure  To Prepare a different solutions Water, PH 1.2 Acidic Buffer, PH 6.8 Phosphate Buffer, PH 7.4 Phosphate Buffer.  The drug material is added in to above solutions till Supersaturated Solution is from.  The Mixture can Placed in Orbital Shaker for 24 hrs. After 24 hrs. Filter the mixture Take Filtrate and Give Absorbance.  To detect the Concentration of Drug is Soluble in Different Solutions. Calibration Curve of Aceclofenac Calibration Curve is determined by using UV Spectrophotometric methods. In which 10 mg drug is added in 100 ml of water (100 μg/ml Solution). To Prepared different Dilutions (0, 2, 4, 6, 8, 10, 12) of above solution (100 μg/ml Solution). Take Absorbance in respective λmax 276 nm. PREFORMULATION STUDIES[16, 17, 18, 19] Drug-Excipient Compatibility Studies Drug is an active part of dosages form and it is mainly responsible for therapeutic value and Excipient substances which are included along with drugs being formulated in a dosage form so as to impart specific qualities to them. It’s also used for development of new drug delivery system as well as investigation of new drug Product. Procedure The Equal portion of Drug and Excipient (1:1 ratio) is added in Ampules and the Ampules are placed in Stability Chamber for one Weak, After One Weak the Drug Excipient Compatibility Study is Determine by using TLC (Thin Layer Chromatography), (n-hexane: Ethyl acetate: acetic acid (7: 0.5: 2.5)), IR (Infrared Spectroscopy) and DSC (Differential Scanning Colariometry). Method of Formulation Aceclofenac Microspheres is prepared by spray-drying Technique. In 1 gm of drug and 1 gm Eudragit RS 30 D, 1 gm Ethyl cellulose (Drug-to-polymer ratio 1:2, 1:3, 1:4, 1:5) is added in 100 ml Iso propyl alcohol (100 ml beaker)., Beaker (100 ml solution) was placed in mechanical stirrer at 5000 rpm, by using spray-dryer apparatus, the solution was fed to the nozzle with a peristaltic pump, atomized by the force of compressed air and blown together with heated air to the chamber where the solvent in the droplets was evaporated. The dried microparticles were harvested from the apparatus collector. All Formulation Ingredients was reported in Table 1 and Parameters for the preparation of microspheres is reported in Table 2. EVALUTION PARAMETERS[20, 21, 22, 23, 24, 25, 26, 27, 28] Particle size analysis Particle size analysis was performed by Motic microscopy method with imaging facility by using advanced Motic digital microscope. Total 200 particles were measured for each formulation and the average particle size was calculated. Encapsulation efficiency Microparticles of sample was weighed and then completely dispersed in distilled water (100 ml (100 ppm solution)), the solution was placed in orbital shaker for 24 hrs. , for complete solubilization of Aceclofenac. After 24 hrs. Sample was filter and take absorbance by using suitable analytical technique (UV spectroscopy) at λmax of 276 nm. And determine Concentration of active constituent in solution. Following formula was used for calculation of encapsulation efficiency. Encapsulation Efficiency % = Practical drug content / Theoretical drug content × 100 In-vitro dissolution testing In vitro study of Aceclofenac microspheres or Microparticles is conducted in pH 6.8 Phosphate buffer was used as a dissolution medium. Microparticles equivalent to 50 mg of Aceclofenac were weighed accurately, and then dispersed into the dialysis membrane. Then the membrane was placed into the basket and rotated at 100rpm. Samples were withdrawn at the time interval of 30, 60, 90, 120, 150 and 180. The volume equivalent to sample withdrawn was replaced by dissolution medium to maintain the sink condition. RESULTS AND DISSCUSION Authentication Parameters Melting Point Method The Melting Point of Aceclofenac is determined by Conventional and Digital Method and Melting Point of Aceclofenac is reported in Table 3.
  3. 3. www.wjpmr.com Savale. World Journal of Pharmaceutical and Medical Research 183 Log P Value Log P Value is determined by Partition Coefficient Phenomenon and Log P Value of Aceclofenac is reported in Table 3. Solubility Studies The Solubility of Aceclofenac in Given Solution. (Water, PH 1.2 Acidic Buffer, PH 6.8 Phosphate Buffer, PH 7.4 Phosphate Buffer) is Reported in Table 4 and Solubility of Pure drug Aceclofenac in Different solvent is shown in Figure 1. Calibration Curve of Aceclofenac in water The Calibration Curve of Aceclofenac is determined by using U.V. Spectroscopic Method. In which the Absorbance of Aceclofenac in Different Concentration (0, 2, 4, 6, 8, 10, and 12) is reported in Table 5. And The Calibration Curve is shown in Figure 2. PREFORMULATION STUDIES The Drug and Excipient Compatibility studies determined by TLC (Thin Layer Chromatography) and IR (Infrared Spectroscopy) Method In which The TLC of Drug, Drug and Excipient before Stability Chamber and After Stability Chamber is reported in Table 6 and TLC (For drug excipient Compatibility) Shown in Figure 3.The IR of Drug taken. The IR Spectra of Pure drug Aceclofenac is shown in Figure 4. The DSC of pure drug Aceclofenac is reported in Figure 5. EVALUTION PARAMETERS Particle size analysis Average particle size was calculated and reported in Table 7. The Particle size is determined by using Motic Microscopy, Digital image of Microsphere was shown in Figure 6. Encapsulation efficiency Encapsulation Efficiency is calculated and reported in Table 7. In-vitro dissolution testing In-vitro dissolution testing of Aceclofenac Microsphere is conducted and reported in Table 7. Table 1: Formulation Ingredients for Preparation of Microsphere. Formulation ingredient F1 F2 Fop Aceclofenac (gm) 0.5 (gm) 0.8 (gm) 1 (gm) Eudragit RS 30 D (gm) 0.5 (gm) 0.8 (gm) 1 (gm) Ethyl cellulose (gm) 0.5 (gm) 0.8 (gm) 1 (gm) Iso Propyl Alcohol (ml) 100 (ml) 100 (ml) 100 (ml) Table 2: Parameters for the preparation of microspheres (Spray dryer Instrument). Parameters Conditions Outlet Temperature 50˚c Inlet temperature 80˚c Plate Temperature 0 Tube Temperature 0 Cool Temperature 80 Drug-to-polymer ratio 1:2, 1:3, 1:4 Feed flow rate 20,30,40, 60, 80 (ml/min) Inlet high 220 Outlet high 160 Aspirator Speed 45-80 Feed Pump 10 Plate Speed 0 D. block on 1 D block off 90 Cycle Time 225 Log Interval 1 Table 3. Melting Point of Aceclofenac Sr.No. Parameters Experimental Result Std. 1 Melting Point (˚c) 151 – 159˚c 152 -153˚c 2 Log p Value 2.16 2.17
  4. 4. www.wjpmr.com Savale. World Journal of Pharmaceutical and Medical Research 184 Table 4: Solubility of Aceclofenac in different solvents. Sr. No. Medium Concentration of drug Soluble (mg /ml) 1 Water 2.01 (mg /ml) 2 PH 1.2 Acidic Buffer 2.80 (mg /ml) 3 PH 6.8 Phosphate Buffer 4.0 (mg /ml) 4 PH 7.4 Phosphate Buffer 4.82 (mg /ml) Result Class of drug BCS Class II Table 5: Calibration of Aceclofenac in Water. Conc(µg/ml) Absorbance 0 0 3 0.148 5 0.246 8 0.434 10 0.535 12 0.632 15 0.808 Table 6: TLC of Drug and Drug: Excipient. Table 7: Evalution of Aceclofenac Microsphere. Experimental parameters F1 F2 FOP Average Particle size (mm) 35.21 25.35 23.9 Encapsulation efficiency (%) 90.56 95.25 98.76 In Vitro Drug Release (%) 92.12 96.52 97.27 Figure 1: Solubility studies in different solvents Sr. No. Samples (Pure From of Drug material) (Drug + Excipient Mixture) Retention factor of drug Before the Stability Chamber Retention factor of drug After the Stability Chamber 1 Pure Drug Aceclofenac 0.76 0.79 2 Aceclofenac + Eudragit RS 30D 0.80 0.81 3 Aceclofenac+ Ethyl cellulose 0.74 0.76 4 Aceclofenac+ Iso Propyl Alcohol 0.70 0.72
  5. 5. www.wjpmr.com Savale. World Journal of Pharmaceutical and Medical Research 185 Figure 2. Calibration curve of Aceclofenac in Water Figure 3: TLC Studies (For Drug: Excipient Compatibility) Figure 4: IR of Pure drug Aceclofenac
  6. 6. www.wjpmr.com Savale. World Journal of Pharmaceutical and Medical Research 186 Figure 5: DSC of Pure drug Aceclofenac. Figure 6: Average Particle size by using Motic Microscopy. Figure 7. In vitro drug release of Aceclofenac in pH 6.8 phosphate buffer (Fop). CONCLUSION Aceclofenac Microsphere is prepared by Spray drying Technique by employing a Eudragit RS 30 D and Ethyl cellulose is responsible for slow release of drug and shows sustained release activity. Particle size and encapsulation Efficiency of the Aceclofenac loaded Eudragit RS 30 D and Ethyl Cellulose microspheres was found to be highly dependent on the Drug-to-polymer ratio and feed flow rate of spray Dryer. The release Microsphere is mainly depended on the composition of Microsphere Formulation Material. The result associated in Optimized batch is good to Satisfactory.
  7. 7. www.wjpmr.com Savale. World Journal of Pharmaceutical and Medical Research 187 ACKNOWLEDGEMENT The authors are grateful to Hon. Principal, SES’s, R. C. Patel Institute of Pharmaceutical Education and Research, Dr. S. J. Surana sir. A special gratitude to Dr. H.S. Mahajan sir Head, Dept. of Pharmaceutics and Quality assurance. Without whom and their constant caring and loving support we would be unable to achieve this advancement and precious stage of our life. REFERENCE 1. Vyas SP, Khar RK. Targeted and Controlled Drug Delivery. Vallabh Prakashan, New Delhi India, 7th Edition., 102-107. 2. Simon B, Eds. Microencapsulation: Methods and Industrial Applications, 2nd ed. Drugs Pharmaceutical Sci. Marcel Dekker, Inc. N.Y., 2006; 158: 1-55. 3. T. Omkar, M. Alagusundaram, S.C. Madhu, Microspheres as anovel drug delivery system, Int J of Chem Tech and Res, 2009; 3(1): 526-534. 4. N.R. Patel, D.A. Patel, P.D Bharadia, V. Pandya, V. Modi. 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