FILTRATION AND CLARIFICATION

DEFINITIONS Filtration: The separation of solid from a fluid by means of a porous medium that retains the solid but allows the fluid to pass. Clarification: This term is applied when solid do not exceed 1.0% and filtrate is the primary product. Ultra-Filtration: Separation of intermicellar liquid from solid by the use of pressure on a semi permeable membrane. Cake Filtration: If recovery of solid is desired, the process is called cake filtration.

Feed or Slurry: The suspension of solid and liquid to be filtered is known as the slurry or feed. Filter Medium: The porous medium used to retain the solids is described as the filter medium. Filter Cake: The accumulation of solids on the filter is referred to as the filter cake. Filtrate: The clear liquid passing through the filter is the filtrate.

TYPES OF FILTER MEDIA Filter paper: Filter paper is a common filter medium since it offers controlled porosity, limited absorption characteristic, and low cost It has different grades and qualities, different pore size such as coarse medium and fine. Disadvantages: They shed very fine particle to the filtrate. Absorb small quantity of liquid.

Woven Material: Cotton, silk, wool, nylon & glass etc. Nylon cloth: Superior to the cotton cloth. Not affected by molds, fungus and bacteria. Has negligible absorption properties. It is extremely strong as compared to cotton cloth. Woven wire cloth: Made from stainless steel. Easily cleaned. Long lasting. Resistant to the chemicals.

Cotton Wool: Commonly used. Small tough of cotton wool placed in the neck of funnel. Glass wool: Use for filtering highly corrosive chemicals. May contaminate the filtrate with glass fibers

Membrane Filter: These are very common among the ultra filtration methods. Made up of cellulose, Polyvinylchloride, Nylon and other cellulose derivatives. They are very fine having a very wide range of pore size from 8µ down to 0.22µ.

Bacteria are removed by sieving Absorption of medicament is negligible Pore size (in µ) Particles removed 0.2 All bacteria 0.45 All coliform group bacteria 0.8 All air born particles 1.2 All Non living particles considered dangerous in I.V. Fluid. 5 All Significant cell from body fluid Advantages: Bacteria are removed by sieving Absorption of medicament is negligible In every new operation, a new disc is used Filtration is quite rapid Don’t liberate particles to the filtrate. Disadvantages: Fine pores may get clogged easily Soluble in certain organic solutions e.g. ketones and esters Very brittle when dry.

FILTRATION EQUIPMENTS Selection of method and equipment required for filtration of a liquid depends on nature of the material and quantity to be filtered as well as the object of the operation.

FILTRATION EQUIPMENTS: FILTER FUNNEL: Funnels are conical shaped devices Made up of Glass, Aluminum, Polythene, Stainless steel OR any other suitable material. Neutral Glass made funnel are most commonly used. White filter paper of suitable pore size is folded in such a way that it fits in the funnel.

BUCHNER FUNNEL: HOT WATER FUNNEL: Made up of porcelain or glass. It has a perforated plate. Used for filtration under reduced pressure. HOT WATER FUNNEL: These are doubled wall funnels made up of metals. Viscous substances such as liquid paraffin, Glycerin, Castor oil and fatty substances like wool fat, bees wax, ointments and cream etc are filtered easily from this filter. Boiling water or steam is circulated in jacketed funnel.

FILTER PRESS: It consists of hollow frames and solid plates. Plates have grooved surface to support the filter cloth. Each plate has an outlet for filtrate. Frames are opened with an inlet for the liquid to be filtered.

Advantages: Construction is very simple. Used for coarse to fine filtration. Operation and maintenance is easy. Filter cloth can be easily replaced. Disadvantages: Not economical for filtration of small quantities Leakage between the plates may take place Suitable when the slurry contain less than 5% solids.

FILTER LEAF: It consists of frame in which drainage screen is enclosed. Whole unit is covered with a filter media. Outlet is connected to the vacuum pump. Frames may be shaped in round, square or rectangular.

Advantages: Disadvantage: Liquid can be filtered form any vessel. Filter cake can be removed simply by washing or blowing air. It is very economical. Disadvantage: It is not effective when solid content in the liquid is more than 5%.

VACUUM FILTRATION : Vacuum filtration is used primarily to collect a desired solid (cake filteration). Vacuum filtration uses a Buchner funnel and a side-arm flask. Vacuum filtration is faster than gravity filtration, because the solvent or solution and air is forced through the filter paper by the application of reduced pressure.

Sterile products

Parenteral Parenteral refers injectable route of administration. It derived from Greek words Para (Outside) and enteron (Intestine). So it is a route of administration other than the oral route. This route of administration bypasses the alimentary canal

PRIMARY PARENTERAL ROUTES Usual volume (mL) Needle commonly used Formulation constraints Types of medication administered SVP Sub cutaneous 0.5-2 5/8 in. , 23 gauge Need to be isotonic Insulin, vaccines Intra muscular 1.5 in. , Can be solutions, emulsions, oils or suspensions Isotonic preferably Nearly all drug classes Intra venous 1-100 Vein puncture 20-22 gauge Solutions, emulsions and liposomes LVP (LARGE VOL. PAR.) 101 and larger (infusion unit) Venoclysis 18-19 gauge Solutions and some emulsions

S. No. ADVANTAGES DISVANTAGES 1. Quick onset Wrong dose or over dose can be fatal 2. Vomiting and unconscious patients can take Pain at site 3. Prolonged action by modified formulation ( Depot) Trained person required 4. Nutritive fluids (glucose, electrolytes) can be given Expensive 5. Drugs with poor absorption or instability from GIT NECESSITY OF ASEPTIC CONDITIONS IN PRODUCTION, COMPOUNDING AND ADMINISTRATION

1. Glass: A. Containers: Highly Resistant Borosilicate Glass Treated Soda lime Glass Regular Soda Lime Glass N.P (Non-parenteral) Glass Type 4 is not used for parenteral packaging, others all are used for parenteral packaging.

2. Plastic: Plastic containers are used but they face following problems Permeation Sorption Leaching Softening 3. Rubber: To provide closure for multiple dose vials, IV fluid bottles, plugs for disposable syringes and bulbs for ophthalmic pipettes, rubber is the material of choice. Problems associated with rubber closures are Incompatibility Chemical instability Physical instability

Intravenous Admixture System “Admixture system” refers to sterile IV solutions that are prepared by using one or more medications or electrolytes and will be administered via the parenteral route. It requires the measured addition of a medication to a 50 ml or larger bag or bottle of IV fluid. It can be provided to the patient in his/her home. Many hospitals involved in compounding IV solutions and medications to patient.

PROCESSING OF PARENTERALS S.No. STEPS 1. Cleaning of containers, closures and equipments 2. Collection of materials 3. Preparation of parenteral products 4. Filtration 5. Filling the preparation in final containers 6. Sealing the containers 7. Sterilization 8. Evaluation of parenteral preparation 9. Labeling and packaging

Formulation of parenteral products In the preparation of parenteral products, the following substances are added to make a stable preparation: The active drug Vehicles Aqueous vehicle (e.g. water for injection, water for injection free from CO2 ) Non-aqueous vehicle (e.g. Ethyl alcohol, propylene glycol, almond oil) Adjuvants Solubilizing agents (e.g. Tweens & polysorbates) Stabilizers & antioxidants (e.g. thiourea, ascorbic acid, tocopherol) Buffering agents (e.g. citric acid, sodium citrate) Antibacterial agents (e.g. benzyl alcohol, metacresol, phenol) Chelating agents (e.g. EDTA) Suspending, emulsifying & wetting agents (e.g. MC, CMC) Tonicity factor (e.g. sodium chloride, dextrose)

Production facilities of parenterals The production area where the parenteral preparation are manufactured can be divided into five sections: Clean-up area Preparation area Aseptic area Quarantine area Finishing & packaging area

Clean-up area: Preparation area: It is not aseptic area. All the parenteral products must be free from foreign particles & microorganism. Clean-up area should be withstand moisture, dust & detergent. This area should be kept clean so that contaminants may not be carried out into aseptic area. Preparation area: In this area the ingredients of the parenteral preparation are mixed & preparation is made for filling operation. It is not essentially aseptic area but strict precautions are required to prevent any contamination from outside.

Aseptic area: The parenteral preparations are filtered, filled into final container & sealed should be in aseptic area. The entry of personnel into aseptic area should be limited & through an air lock. Ceiling, wall & floor of that area should be sealed & painted. The air in the aseptic area should be free from fibers, dust and microorganism. The High efficiency particulate air filters (HEPA) is used for air. UV lamps are fitted in order to maintain sterility.

Quarantine area: Finishing & packaging area: After filling, sealing & sterilization, the parenteral product are held up in quarantine area. Randomly samples were kept for evaluation. The batch or product pass the evaluation tests are transfer in to finishing or packaging area. Finishing & packaging area: Parenteral products are properly labelled and packed. Properly packing is essential to provide protection against physical damage. The labelled container should be packed in cardboard or plastic container. Ampoules should be packed in partitioned boxes

EVALUATION OF PARENTERAL PREPARATIONS The finished parenteral products are subjected to the following tests, in order to maintain quality control: A) Sterility test B)Clarity test C)Leakage test D)Pyrogen test 1) rabbit method 2)LAL test (Limulus amebocyte lysate) E)Assay

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