463 PHT Compendia requirement for Semi solid

1. 463 PHT Compendia requirement for Semi solid

2. Ideal properties of semi-solid dosage forms • Physical properties • a)Smooth texture • b)Elegant in appearance • c)Non dehydrating • d)Non gritty • e)Non greasy and non staining • f)Non hygroscopic

3. Physiological properties • g)Non irritating • h)Do not alter membrane / skin functioning • i)Miscible with skin secretion • j)Have low sensitization index • K)APPLICATION PROPERTIES: - • L)Easily applicable with efficient drug release. • M)High aqueous washability.

4. Storage properties • Stable under various real world storage conditions as per ICH guidelines. • Storage of semisolids should be at temperatures not exceeding 25° unless otherwise authorized. • They should not be allowed to freeze and must be stored in a well-closed container or, if the preparation contains water or other volatile ingredients, store in an air-tight container. • The containers are preferably collapsible metal tubes from which the preparation may be readily extruded. • If the preparation is sterile, store in a sterile, airtight, tamper-proof container.

5. Microbial content • Minimum fill • Packaging • Storage • Labeling • Sterility

6. Microbial content • These products should meet the acceptable standards for microbial content • Microbial limits are stated for each preparation in the USP • Ex. Betamethazone valerate oint. USP Must meet the requirement of test for absence of Staph and Pseudo. Aeruginisa • These organisms have capacity to infect the skin

7. To minimize both the type and the number of microorganisms in unsterilized pharmaceutical product, there should be strict adherence to environmental control and application of good manufacturing practice • Dermatological product should be examined for P. aeruginosa and S. aureus • Rectal, urethral, or vaginal product should be tested for yeast, moulds because they are common offender at these sites

8. Test raw material • Use of acceptable water • In process control • Final product testing • The USP stated that certain products should be routinely tested for microorganism because the way they are used

9. Procedure • 10 gm or 10 ml of the products is tested after suitable dilution and added to a specific media and incubate between 30-35 °C for 24-48 h • For purpose of confirming a doubtful result, a retest on 25 gm specimen of the product may be conducted.

10. Minimum Fill • Select 10 filled containers, remove any labeling. • Clean and dry the outside of the containers, and weigh individually. • Quantitatively remove the contents from each container, cutting the latter open and wash with a solvent. • Dry and weigh again each empty container. • The difference between the two weights is the net weight of the contents:

11. The average net content of the 10 containers is not less than the labeled amount, and the net content of any single container is not less than 90% of the labeled amount where the labeled amount is 60 g or 60 ml or less . • Or not less than 95% of the labeled amount where the content is 60 g/or ml – 150 g /or ml. • If this requirement is not met, determine the content of 20 additional containers.

12. The average content of the 30 containers is not less than the labeled amount, and the content of not more than 1of the 30 containers is less than 90 % of the labeled amount where the labeled amount is 60 g or 60 ml or less . • or not less than 95% of the labeled amount where the content is 60 g/or ml – 150 g /or ml.

13. Leakage test • - Select 10 sealed tubes of the ointment • - Clean and dry the exterior surfaces • - Place the tubes with an absorbent sheet in oven at 60 C ± 3 for 8 hours • - If leakage is observed from one, but not more than one, of the tubes, repeat the test with 20 additional tubes • - The requirement is met if no leakage is observed from the first 10 tubes, or if leakage is observed from not more than 1 of 30 tubes tested.

14. Ointments and other semisolids are packed in : • Large-mouth jar • Metal or plastic tubes • Well closed containers to protect against contamination • Cool place to protect against product separation by heat • When requires light resistance or opaque container for light sensitive drugs • In addition to the usual labeling, the USP directs that for certain ointments and creams include the type of base used either water soluble or water insoluble

15. Additional standards • To ensure within lot-to-lot uniformity; • Viscosity • In vitro release • Texture: feel upon application (grittiness) • Particle size distribution • pH, odour, colour

16. Ophthalmic Dosage Forms • Solutions: are sterile solutions essentially free from foreign particles, suitably compounded and packaged for instillation into the eyes • Suspensions: are sterile liquid preparations containing solid particles dispersed in a liquid vehicle. (insoluble solids must be microfine). • Ointments: Are dispersions of medicinal substances in petrolatum. A particular requirement of ophthalmic ointments is that of “spreadability • Ocular therapeutic system: ocusert

17. Design of product quality: product design concepts together with quality assurance concepts must be developed with ophthalmic sensitivity as a major consideration General considerations • Raw materials: The selection of specific raw materials should include specifications which assure batch-to-batch reproducibility of product quality. Particle size is necessary

18. Particulates: The USP definition of an ophthalmic product include the phrase: “free from foreign particles” • Solution clarity is a requirement (by filtration) • It is equally important to fill into particle-free containers • Glass or plastic containers are normally washed, rinsed with purified water, finally rinsed with filtered, particulate-free purified water, then dried and sterilized • The filling operation is carried out in an atmosphere controlled by laminar flow air control • The standard of Class 100 clean room should apply to the manufacture of ophthalmic products

19. Formulation aspects • The formulation of ophthalmic solution requires consideration of : • Drug solubility • Buffer , pH • Tonicity • Clarity Viscosity • Antimicrobial preservation • Safety sterility • Stability

20. Metal Particle in ophthalmic ointments • Extrude as completely as practicable, the content of 10 tubes individually into separate clear flat-bottom, 60 mm Petri dish. • Cover the dishes and heat at 85 C for 2 h, to ensure that a fully state is obtained. • Allow sample to cool to room temp. and to solidify • Remove the cover and invert the Petri dish on the stage of a microscope equipped with eye-piece micrometer disk, direct an illuminator above the ointment at 45 angle.

21. Examine the entire bottom of the Petri dish for metal particles. • Count the number of metal particles that are 50 μm or larger . • The requirement are met if the total number of such particles in all 10 tubes does not exceed 50, and if not more than 1 tube is found to contain more than 8 such particles. • Repeat the test on 20 additional tubes, • if the total number of metal particles (50 μm or larger) does not exceed 150 in all 30 tubes tested, and if not more than 3 of the tubes contain more than 8 such particles each.

22. Packaging , storage and labelling • Ophthalmic products are contained in low-density polyethylene dropper bottles, glass bottles with dropper, or ointment tubes with an extended tip • Polyethylene is not well suited as a container for easily oxidized substances • It can not be heat sterilized • Ethylene oxide is used as a sterilant • Adequate control of packaging materials is essential to product quality