Impact factor: /ICV: PROCESS VALIDATION OF PARACETAMOL SUSPENSION Sisal Shah*, Dinesh G. Desai, A. K.

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1 Impact factor:.3397/icv: Pharma Science Monitor 6(2), Apr-Jun 25 PHARMA SCIENCE MONITOR AN INTERNATIONAL JOURNAL OF PHARMACEUTICAL SCIENCES Journal home page: PROCESS VALIDATION OF PARACETAMOL SUSPENSION Sisal Shah*, Dinesh G. Desai, A. K. Seth, Ronak Patel Department of pharmacy, Sumandeep Vidyapeeth, At & Po piparia, Ta-Waghodia, Dist-Vadodara-3976 ABSTRACT The present study was to validate the paracetamol suspension with the combination of tragacanth (.2%) and Na.CMC (.%) for different mixing speed and time, the fast speed with 5 minutes showed the most satisfactory results. Hence, it can be recommended that, the same parameters shall be considered as final for further commercial routine production batches of paracetamol suspension. KEYWORDS: Process Validation, Paracetamol suspension, Prospective study. INTRODUCTION PROCESS VALIDATION [, 2] Validation is establishing documented evidence which provides a high degree of assurance that a specific system will consistently produce a product meeting its predetermined specifications and quality attributes. "PROCESS VALIDATION" is establishing documented evidence which provides a high degree of assurance that a specific process consistently produces a product meeting its predetermined specifications and quality attributes" Importance of Process Validation [3, 4] Enhances the ability to evaluate process performance and product variables. Enhances evaluation capabilities and increases confidence about process reproducibility and product quality. Improves ability to set target parameters and control limits for routine production, correlating with validation results. Decreases the errors in production Assurance of quality Cost reduction Government regulation

2 Impact factor:.3397/icv: 4. 3 TYPES OF PROCESS VALIDATION ) Prospective process validation 2) Concurrent process validation 3) Retrospective process validation 4) Revalidation [5, 6] MATERIALS AND METHOD: Table no: List of materials SR NO. NAME OF MATERIAL NAME OF SUPPLIERS Paracetamol Shine Pharmaceuticals Karjan, Vadodara. 2 Na.cmc, Tragacanth, Acacia Suvidha Lab. Vadodara. 3 Purified Water SumandeepVidyapeeth 4 Sodium methyl paraben Shine Pharmaceuticals Karjan, Vadodara. 5 Glycerin Aatur Lab. Vadodara 6 Sorbitol 7% solution Drug Profile: Table no2: Drug Profile [7, 8] Name of Drug Paracetamol Molecular Weight : 5.69 g/mol IUPAC Name N-(4-hydroxyphenyl) acetamide Molecular Formula C 8 H 9 NO 2 Molecular Structure Solubility Insoluble in water, Freely soluble in methanol, Soluble in alcohol Melting Range C Storage Protect from light at room temperature. Category Analgesic and Antipyretic Appearance Stability Onset of action White Crystalline Powder Stable, not hygroscopic.5 to hour

3 Impact factor:.3397/icv: 4. 3 Methods:. Preformulation: [9] It is the first step in rational development of dosage forms of drug substance. Preformulation testing is defined as investigation of physical and chemical properties of a drug substance alone and when combined with excipients. The overall objective of preformulation testing is to generate information useful to the formulator in developing stable and bioavailable dosage forms that can be mass-produced. Following preformulation was study check on paracetamol Suspension.. Colour, odour and appearance: The drug sample was evaluated for its colour and odour..2 Determination of λ max: [] 25 mg of drug was first dissolved in 25 ml of. M NaOH and obtained a stock solution of µg/ml concentration. Then from the stock solution ml was pipette out and diluted with. M NaOH which gave µg/ml concentrations. And from the above solution ml was pipette out and diluted up to ml with. M NaOH solution and produced aliquots of different concentrations like µg/ml, 2 µg/ml, 3 µg/ml, 4 µg/ml, 5 µg/ml, 6 µg/ml. 7 µg/ml. 8 µg/ml, 9 µg/ml, µg/ml. The solutions were scanned in spectrum mode for absorbance of 257 nm using spectrophotometer. 2. Preparation of calibration curve of drug: 2. Assay of paracetamol with. N NaOH: [] Procedure: Weigh accurately about.5 gm of PCM, add 5 ml of. M NaOH, dilute with ml water, shake for 5 minutes and add sufficient water to produce 2 ml. mix, filter and dilute ml of the filtrate to ml with water. To ml of resulting solution add ml of. M NaOH dilute to ml with water and mix. Measure the absorbance of resulting solution at maximum of about 257nm. 3. Formulation of suspension: METHOD (l) Paracetamol was accurately weighed, water was added and triturated in a mortar pestle. Mucilage of suspending agent was added (which was prepared in small quantity of water, triturated and kept overnight). Sodium citrate as well as sodium methyl paraben was dissolved in small quantity of water. Both the solutions were added in mortar. Triturated well.

4 Impact factor:.3397/icv: Glycerin and 7% sorbitol solution were added in it. Transfered into measuring cylinder. Sucrose syrup was added and purified water was added to make up the volume. HOMOGENIZATION WAS DONE AT: TIME- 5 MIN SPEED- MEDIUM SPEED METHOD (II) Triturate PCM and mucilage of suspending agent (prepared and kept overnight). Dissolve sodium citrate as well as sodium methyl paraben in small quantity of water. Add both solutions in mortar. Triturate well. Add glycerin and 7% sorbitol solution in it. Transfer into measuring cylinder and add sucrose syrup and make up the volume with purified water. HOMOGENIZATION WAS DONE ON BASIS OF TIME AND SPEED. TIME- 5 MIN SPEED- MEDIUM SPEED 4. Validation: Table no3: Variables VARIABLES MIXING SPEED MIXING TIME (Min) Fast Medium Slow 5,, 5, 2 5,, 5 5,,5 5. Stability studies: The stability study was carried out for optimized formulation as per ICH guidelines (Feb. 23). Various ICH storage conditions are available which are as 2-8 c ± 75% RH and at room temperature for six weeks.

5 Impact factor:.3397/icv: SELECTED FORMULA Table no 4: Formula Ingredient Quantity Given Quantity in grams for 5ml Paracetamol 25mg/5ml 25 gm Sodium Citrate.5% 2.5 gm Sorbitol 7% % 5 ml Glycerine % 5 ml Sucrose Syrup 4% 2 ml Tragacanth.2% gm Na. CMC.% 5 gm Sodium Methyl Paraben.2% gm Purified Water Q.S. Q.S. VARIABLES FOR VALIDATION Further validation of paracetamol suspension with the combination of Na. CMC.% + Tragacanth.2% was carried out. Fast speed Mixing Particle Viscosity Density Redispersibility Assay Time size (µm) (cps) (gm/cm 3 ) (No. of times) (%) (Min)

6 Impact factor:.3397/icv: Batch A (a) Fast min Batch A (b) Fast min Batch A (c) Fast 5 min Hu/H Batch A (d) FAST 2 MIN OBSERVATION The suspension with fast 5 minutes was selected because this suspension showed better results for particle size, good redispersibility, highest volume of sediment, assay and slow sedimentation rate as compared to other suspensions for same speed (Fast). MEDIUM SPEED Batch No. Mixing time (Min) Particle size (µm) Viscosity (cps) Density (gm/cm 3 ) Redispersibility (No. Of times) A(e) Assay (%) A(f) A(g)

7 Impact factor:.3397/icv: Hu/Ho Batch A (e) Medium 5 min Hu/Ho.2 Batch A (f) Medium min Batch A (g) Medium 5 min OBSERVATION At constant speed-slow and variation in time, Batch A (k) showed better when compared with other batches on the basis of: PARAMETERS Sedimentation rate Redispersibility Assay OBSERVATION.7 4 times inversion 97% Slow speed Variable for constant time and variation in speed Speed Mixing Time (Min) Particle size (µm) Viscosity (cps) Density (gm/cm 3 ) Redispersibility (No. of inversions) Assay (%) Slow Medium Fast When it was compared on the basis of constant time of 5 Time minutes and variation in speed Fast 5 minutes Batch A(c) was selected because of following results:

8 Impact factor:.3397/icv: PARAMETERS OBSERVATION Sedimentation rate.37 Redispersibility Twice Assay 99.5% Stability Study: Stability study of Paracetamol Suspension was carried out. Physical Stability (initial) Condition PH( ) Color (White) Assay Redispersibility Initial After Initial After (By Inversion) Refrigeration White White 98% 2 (2-8 c) Room Temperature White White 98.9% 2 Physical Stability (After 6 Weeks) Condition PH ( ) Color (White) Assay Redispersibility Initial After Initial After (By Inversion) Refrigeration White White 98.3% 2 (2-8 c) Room Temperature White White 97.6% 2 Physical Stability (After 2 Weeks) Condition PH ( ) Color (White) Assay Redispersibility Initial After Initial After (By Inversion) Refrigeration White White 98.5% 2 (2-8 c) Room Temperature White White 98.9% 2 DISCUSSION When the combined effect of two suspending agents was studied it was found that the combination of sodium CMC.% + Tragacanth.2% gave the satisfactory results. Further, validation was carried out on the optimized Batch A i.e. sodium CMC.% + Tragacanth.2% on the basis of change in methodology, mixing speed and mixing time. In case of change in method- Method showed the satisfactory results like slow sedimentation rate, good redispersibility, assay and higher volume of sediment.

9 Impact factor:.3397/icv: Next validated parameters were mixing speed and mixing time. Batch A (c) at fast speed for 5 time minutes was optimized on the basis of slow sedimentation rate, good redispersibility, assay and higher volume of sediment. SUMMARY The formulation was validated by mixing speed, mixing time and change in methods. It was observed that homogenization at fast speed for 5 minutes gave desired results. The formulation was also kept under stability conditions and it was found to be stable. CONCLUSION The present work demonstrated that paracetamol suspension 25mg/5ml was prepared using combined form of suspending agents resulted in slow sedimentation rate, good redispersibility and higher volume of sediment. Thus, it has been concluded that combination of.2% w/v tragacanth +.% w/v Na. CMC showed consistent superiority over other suspensions. This formulation was further validated for certain parameters like mixing speed, mixing time and change in methods. Homogenization at fast speed for 5 minutes time gave desired results. The formulation was also kept on stability and it was found stable. REFERENCES. U.S. Food and Drug Administration. Guidelines on general principles of process validation. Rockville, MD: Division of Manufacturing and Product quality, centre for drugs and biologics 987; Nash RA, Watcher H. Textbook of Pharmaceutical Process Validation. 7 th Edition. New York, Marcel Dekker, Inc., 2; Gupta S, Saini S, Singh G, Rana A. An overview on Industrial Process Validation of Tablet Dosage Form. IRJP 22; 3(3): Gupta GD, Garg R, Agrawal S. Guidelines on General Principles of Validation: Solid, Liquid and Sterile dosage forms, 2 nd edition. London, Taylor and Francis Group publishers. 28; 6: Lambert J. Validation Guidelines for Pharmaceutical Dosage Forms. Health Canada/Health Products and Food Branch Inspectorate, 24; Nash RA, Wachter H. Textbook of Pharmaceutical Process Validation. 3 rd Edition. New York, Marcel Dekkar, 23: Vincent D. Validation technology. Centre for drug evaluation and research (CDER) 2; 8: Indian Pharmacopoeia. Mumbai, Indian drug manufacture association, 22; 3: 54-5.

10 Impact factor:.3397/icv: Subramanyam C.V.S. Text Book of Physical Pharamaceutics. Second edition. New Delhi, Vallabh Prakashan, 28; Indian Pharmacopoeia. Mumbai, Indian drug manufacture association, 22; 3: Indian Pharmacopoeia. Mumbai, Indian drug manufacture association, 22; : 6 For Correspondence Sisal Shah sisalshah@gmail.com