OINTMENT ASEPTIC MANUFACTURING, IPQC & PROCESS AUTOMATION IN SEMISOLIDS
- 1. IPQC TEST OF OINTMENT PROCESS AUTOMATION IN: SEMISOLIDS Name : Akanksha B. Puri Roll No : 01 Quality Assurance Techniques
- 2. CONTENT Process automation in semisolids Introduction Types Manufacturing process IPQC test
- 3. PROCESS AUTOMATION IN SEMISOLIDS What is automation? • Automation is the use of machines to complete the majority of repeatable and significant tasks in the pharmaceutical industry. • There has been a faster rate of industry development, and the pharmaceutical sectors are no exception. • A process automation or automation system(PAS) is used to autonomously control a process Objectives 1) Enhancing the Productivity of manufacture 2) Robots can easily complete repetitive actions like filling, packing at higher precision 3) Need to achieve consistent quality product
- 4. PHARMACEUTICAL PROCESSING EQUIPMENT Equipment for pharmaceutical processing and packaging is utilised for a variety of tasks, including filling, counting and labelling as well as processing tasks like blending, mixing, granulating, milling, cleaning and sterilizing. Automation is the employment of tools and machinery in lieu of people to carry out physical and mental tasks during the production process. There are several different types of equipment for distinct unit processes in pharmaceutical production, including:
- 5. • Sterile semisolids Automation Lid lifting provided with hydraulic system. Contra rotary agitator for high viscosity products. Integrated cleaning system for CIP and SIP Load cell on respective vessels PLC based control for complete automation of process, recipe administrator and visualization. Here in this case, the equipment is functionally safe and easy to operate and has no manual handling. Thorough-washing of cake can be done as well as toxic and hazardous material can be processed. Product purity can be maintained. Blending of product possible before discharging
- 6. Unit operations of semisolids Tank filled agitator for mixing of liquid Tumble blender for mixing of solids and semisolids Hammer mill for milling and size reduction of solid and semisolids.
- 7. Closed system can be designed to ensure maximum solvent collection for recovery Agitator impellers Combination of filtration, washing, re- slurring, "drying in enclosed automated unit processed faster than the conventional systems small filtration area to large size • Complete Automation
- 9. • Ointments are homogenous, translucent, viscous semisolid preparations, most commonly a greasy thick oil (oil 80%- water 20%) intended for external application to the skin or mucus membrane . • Drug ingredients can be dissolved, emulsified or suspended in ointment base. • The word ointment comes from the latin meaning anoint with oil. INTRODUCTION
- 10. TYPES OF OINTMENT UNMEDICATED OINTMENTS 1) Petroleum jelly MEDICATED OINTMENTS 1)Dermatological ointment 2) Ophthalmic ointment 3) Rectal ointment 4) Vaginal ointment 5) Nasal ointment
- 11. MANUFACTURING PROCESS Preparation of ointment can be done by; Mechanical incorporation: 1) Trituration method 2) Emulsification method 3) Mixing method (in large scale done by different equipment like roller mill, Hobart mixer) 4) Fusion method 5) Chemical Reaction Method
- 12. 1) TRITURATION METHOD SIZE REDUCTION LEVIGATION MIXING WITH BASE SPATULATION OR TRITURATION MIXING BASE TO PRODUCE FINAL WEIGHT HOMOGENIZATION FILLING
- 13. 2) EMULSIFICATION METHOD All the ingredients are taken in their required quantity The fats , oil and waxes are melted together on water bath at a temperature of 70ºC The aqueous solution of all heat stable component are heated at same temperature. The solution is slowly added to melted bases with continuous stirring until cool down and semi-solid mass known as ointment prepared
- 14. 3) FUSION METHOD When ointment contains a number of solid ingredient with different melting point , it is necessary to melt them in decreasing order to their melting point. All the components are melted accordingly The medicaments are slowly added to melted stirred thoroughly until mass cool down and gives homogenous mixture.
- 15. QUALITY CONTROL TESTS FOR OINTMENTS UNIVERSAL TEST SPECIAL TEST SPECIFIC TEST DESCRIPTION IDENTIFICATION ASSAY IMPURITIES PHASE SEPARATION UNIFORMITY IN CONTAINER LEAKAGE TEST PH HOMOGEINITY SENSITIVITY PARTICLE SIZE WT. VARIATION SPREADABILITY STERILITY TEST
- 16. 1. UNIVERSAL TEST a) Description: This includes a visual examination to identify changes in color, separation, and crystallization in the final appearance of the product. The description should specify the content or label claim of the product. b) Identification: Quantitative identification of active ingredients in the finished dosage form. Methods: • IR • Raman spectroscopy • chromatography
- 17. c) Assay: The quantity of drug present in unit weight or volume of ointment is determined by: • Spectrophotometric method • Titrimetric method • Chromatographic method • Microbial assay Detected by UV By using RP-columns Chromatographic separation Formulation matrix Extract drug with solvents
- 18. d) Impurities: The impurities arising from the degradation of drug substances and during the manufacturing process of the drug product should be assessed and controlled. on 14th day No. of vegetative cells NMT 0.1% of initial conc On 28th day No. of organisms should be below or equal to initial conc.
- 19. II.SPECIFIC TESTS 1.PH From the following standpoint, the pH of a formulation must be considered. a. The effect on the body when the formulation is applied b. The effect on stability of the product c. The effect on container-closure system • pH meter is initially calibrated with respective buffer capsule (pH 4,7 & 9) then the pH of the preparation is measured. • The pH of formulations were determined by using digital pH meter. • 1 gm of ointment was dissolved in 100ml of distilled water & stored for 2 hours. The measurement of pH was determined.
- 20. 2. HOMOGEINITY • Content of ointment is placed on glass slab and spread in form of thin layer, Observe under light source • Acceptence criteria - Ointment is homogenous if there is no granules present 3. SENSITIVITY TEST • In this, when we use various types of ingredients with occasional use of antiseptics hormones etc, there is a possibility of occurrence of sensitization or photosensitization of the skin. • This should be tested beforehand. This test is generally done by patch test. • At different places the test sample is applied along with a standard market product & after a period of time effect is compared.
- 21. 4. PARTICLE SIZE DETERMINATION • Dilute preparation with equal volume of glycerol/liquid paraffin as per monograph. • Mount on glass slide. • Observe through microscope. • Calculate the no. of particles having max., diameter within stated limit Acceptance rejection criteria Diameter of particles ≥10 µm ≥25 µm ≥50 µm No. of particles Not more than 12/ml Not more than 5/ml Not more than 2/ml
- 22. 5. SPREADABILITY • Spreadability of the formulations was identified by measuring the spreading diameter. • To determine the Spreadability the ointment formulation of 1gm was placed between the horizontal plates (20×20 cm²). After 1 minute, the upper plate was tied with a standardized weight of 125gm. • The time in which the upper glass slide moves over to the lower plate was taken as measure of spreadability.
- 23. 6. WEIGHT VARIATION OR MINIMUM FILL • Test is applied only to those containers that contain not more than 150 g or ml of preparation. • Select filled containers, remove label and weight them individually • Remove the contents and weigh the empty containers Individually • Take difference of full and empty container for getting content. Acceptance/rejection criteria: • Take average of 10 containers which should not be less than labelled amount • Performance in 2 stages, in S1 select 10 units if not meet criteria then on S2 select 20 more unit and total units is 30.
- 24. Sample size S1= for 10 unit S2= for 30 For ≤60g Net wt of contents of any single unit should not be less than 90% of the labelled amount Net wt of contents of not more than 3 units should be less than 90% of labelled amount. For 60-150g Net wt of contents of any single unit should not less than 95% of the labelled amount Net wt of contents of not more than 1 unit should be less than 95% of labelled amount
- 25. 7. RATE OF ABSORPTION • The evaluation should be performed on ointment for the rate of absorption of drug into the blood stream. The rate of absorption test can be run in-vivo only. • Definite amount of ointments should be rubbed through the skin under standard conditions as well as medicaments are estimated in the blood plasma or urine. 8. EXTRUDABILITY • To determine the Extrudability of formulation the metal or aluminum collapsible tube was filled with ointment formulation & the pressure was applied to the tube so that extrusion of ointment takes place & it was checked
- 26. SPECIAL TESTS FOR SEMISOLID DOSAGE FORMS: 1. PHASE SEPARATION TEST: • Visual tests • Done by measuring the volume of separated phases. 2. RHEOLOGY & VISCOSITY • Ointments are marketed in tubes or containers so rheology is very important. • The rheology or viscosity should remain constant. • It can be measured using viscometers for non-Newtonian products. • Rheological measurements are used to the ease of bottle pouring, squeezing from a tube container, & maintaining product shape in a jar.
- 27. 3. Microbial content & Sterility test a) Membrane filtration method • In the membrane filtration method, a solution of test product (1%) is prepared in isopropyl myristate and allowed to penetrate through cellulose nitrate filter with pore size less than 0.45µm • In necessary, gradual suction or pressure is applied to aid filtration. • The membrane is then washed three times with 100-ml quantities of sterile diluting and rinsing fluid and transferred aseptically into fluid thioglycolate (FTG) and soybean - casein digest (SBCD) medium. • The membrane is finally incubated for 14 days. • Growth on FTG medium indicates the presence of anaerobic and aerobic bacteria, and SBCD medium indicates fungi and aerobic bacteria. • Absence of any growth in both these media establishes the sterility of product
- 28. b) Direct inoculation method • In the direct - inoculation technique, I part of the product in diluted with 10 parts of sterile diluting and rinsing fluid with the help of an emulsifying agent. • Incubated in FTG and SBCD media for 14 days. • Criteria: In both techniques, the number of test articles is based on the batch size of the product. If the batch size is less than 200 the containers, either 5% of the containers or 2 containers (whichever is greater) are used. If the batch size is more than 200, 10 containers are used for sterility testing. • Acceptance rejection criteria: If no evidence of microbial growth, sample is sterile. If evidence of microbial growth, sample is non sterile
- 29. 4. Metal particle test • This test is required ONLY for ophthalmic ointments, performed using 10 ointment tubes • The content from each tube is completely removed onto a clean 60-mm-diameter petri dish • The lid is closed and the product is heated at 85° C for 2 h. • Once the product is melted and distributed uniformly, It is cooled to room temperature. The lid is removed after solidification. • The bottom surface is then viewed through an optical microscope at 30 magnification. The viewing surface is illuminated using an external light source positioned at 45°on the top. • The entire bottom surface of the ointment is examined, and the number of particles are 50µm or above counted using a calibrated eyepiece micrometer • Acceptance rejection criteria: • The number of such particles in 10 tubes should not exceed 50. with not more than 8 particles in any Individual tube. • If these limit not met the test is repeated with an additional 20 tubes
- 30. 5. Leakage test • This test is mandatory for ophthalmic ointments, which evaluates the Intactness of the ointment tube and its seal. • 10 sealed containers are selected, and their exterior surfaces are cleaned. • They are horizontally placed over absorbent blotting paper and maintained at 60% 3° C for 8 hr • Acceptance rejection criteria The test passes if leakage is not observed from any tube. If leakage is observed, the test is repeated with an additional 20 tubes. The test passes if not more than 1 tube shows leakage out of 30 tubes.
- 31. 6. Potency/content uniformity test In this test the different analytical techniques are used as per the Individual monograph • Assay the 10 units individually, if test failed 20 more containers are tested. • Drug assay is performed by using different analytical techniques e.g. titrimetric assay. • Conduct the assay on the amount of the material that drains from the individual container. Acceptance rejection criteria For 10 doses unit acceptance criteria: Not more than 1 individual content, is outside the limit of 85%-115% of average labelled amount. Not a single unit should be outside the limit of 75%-125% of average labelled amount. If this step rejects then take 20 more units and test individually. For 30 unit acceptance criteria: Not more than 3 units are outside the 85%- 115% of average labelled amount No one is outside the 75%-125% of average content.
- 32. REFERENCES 1. Indian Pharmacopoeia, 2014, volume-2, The Government of India, Ministry of Health and Family Welfare, New Delhi, pp: 951-952 2. Jadhav Ankush P., Kedar Tejashree R., Datar Prasanna A., Jagtap Rushikesh N., & Jadhav Ravindra T., "New Approaches for Evaluation Test of Pharmaceutical Dosage Forms", International Journal for Research Trends and Innovation, 2020, Volume 5, Issue 10, 47-48.
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