Manufacturing Methods of Suppositories

Transcription

1 Manufacturing Methods of Suppositories 1- Hand rolling method:classification of Suppositories Based on molding suppositories with fingers after the formation of a plastic mass In mortar add:- 1- A plastic-like mass is prepared by triturating grated cocoa butter & active ingredients in a mortar. 2- Pestle should be used to force the mass together against the sides of the mortar. To form plastic mass (It may be warmed very gently temp below 30 o C. 4- Cohesive mass is rolled into cylinder. 5- The total mass is weighed to record the total weight. (the mass is divided into the No. of the dose.) 6- The mass will quickly solidify & lose it plasticity) 7- The cone & pointed cylinder are the shapes that easily formed by hand rolling procedure. 8- Wrapped & packed. 2-Compression method Based on forcing suppository Base & medicaments into special compression mold. 3-Fusion method 1-Based on melting the suppository base (vehicle) & then disperse or dissolve the drug in the melted base. 2- pour the mixture into mold. Allow it to congeal. 3- remove from mold. Quality Control Tests QUALITY CONTROL procedures listed in the US Pharmacopeia (USP30-NF25) for manufactured suppositories include identification, assay, and, in some cases, NOTES NOTES Pharmaceutics III Page 1

2 water content, residual solvent, dissolution, and content uniformity 1- Appearance of suppository, include odor, color, surface condition & shape. 2- Content uniformity : to ensure that each individual supp. contains the labeled content 3-Weight variation: should be within 5% 4- Melting point/melting Zone: Macro-melting point test :- is a measure of the time needed for the entire suppository to melt when immersed in a constant-temp. at 37 C water bath. Micro-melting point:- is the melting range measured in capillary tubes for the base only. 5-Breaking test (fragility test) Is the test that carried out to measure the brittleness or fragility of suppository. Erweka hardness tester-is used to determine the weight at which the suppository collapse. 6- Dissolution rate The in-vitro release pattern is measured. The volume surrounding suppository is constant & the drug content is measured at different intervals The time versus drug concentration can be obtained. Pharmaceutics III Page 2

3 7- Liquefaction time Liquefaction testing provides information on the behavior of a suppository when subjected to a maximum temperature of 37 C. The test commonly used is Krowczynski s method, which measures the time required for a suppository to liquefy under pressures similar to those found in the rectum in the presence of water at 37 C. In general, liquefaction should take no longer than about 30 minutes. 8- Melting and solidification time There is a relationship between melting and solidification that is important to characterize. The release of the active ingredient from the vehicle is related to the melting point of the vehicle and the solubility of the drug in the vehicle. Suppositories undergo three changes in phase during their life. First, they are melted and then solidified; upon administration, they are again melted. An understanding of these factors and their relationships is critical for evaluating the bioavailability of the final suppository formulation. The higher the melting point, the later the drug effects appear. If too high, the drug effect does not appear. Various methods are available to measure it, including Shukoff s method, the European Pharmacopoeia also describes a procedure. Pharmaceutics III Page 3

4 Sterile Products Sterile Pharmaceutical Products Parenterals Ophthalmic preparations Radiopharmaceutical preparations They are sterile products intended for administration by injection under or through the skin or directly into body fluids, tissue or organs Sterile- free from any contaminating microorganism Small Volume Parenterals or Large Volume Parenterals Physiology:- Located outside the alimentary canal. Disadvantage Pain and discomfort Incorrect drug dose ( impossible to overcome the error Restricted to hospital or specialized personnel ROUTE OF PARENTERAL ADMINISTRATION In pharmacology and toxicology, a route of administration means the path by which a drug, fluid, poison or other substance is brought into contact with the body. Parenteral by injection or infusion 1- Subcutaneous injections NOTES Pharmaceutics III Page 4

5 Injecting a fluid or a solid pellet into the layer of loose connective and adipose tissue directly underlying two outer layers ( epidermis and dermis) of the skin. injections are used to administer vaccines and medications, A pellet may be injected to deliver longlasting doses of medication Common drugs for this route are vaccines, insulin, and epinepherine Drugs by this route have a slow onset of action than an IM or IV Following administration, the site of injection, the body temperature, age, degree of massage at the injection site are factors affecting drug distribution. NOTES Pharmaceutics III Page 5

6 The injection of a substance directly into a relaxed muscle. It is used for particular forms of medication that are administered in small amounts. Intramuscular injections are often given in the: Deltoid muscle in the shoulder (for rapid absorption of drug) astus lateralis muscle of the thigh entrogluteal and dorsogluteal muscles in the buttock Deltoid muscle :- thick, flat triangular muscle responsible for the round shape of the shoulder. Vastus lateralis muscle NOTES Pharmaceutics III Page 6

7 Ventrogluteal muscles Dorsogluteal muscles IM injections are preferred to be isotonic Absorption is relatively rapid compared to SC. Pharmaceutics III Page 7

8 For SC or IM injection there is a delay in the systemic effects of the drug (the drug first has to pass through the epithelial cells & the capillaries walls before entering into the blood. This occurs by passive diffusion. 3- Intravenous injections - Volume varies from less 1 ml- 500 ml. Giving of liquid substances directly into a vein into blood for a faster effect. The word intravenous simply means "within a vein". IV rapidly increases the concentration of the drug in the blood plasma, but the concentration soon falls due to reversible transfer of the drug from plasma into body tissue (Process of drug distribution). That followed by irreversible excretion and metabolism Pharmaceutics III Page 8

9 IV products are usually aqueous or hydroalcoholic solutions O/W emulsion with controlled particle size can be used Volume less than 10 ml is termed intravenous BOLUS Advantage 100 % bioavailability Rapid response Plasma concentration after 4 mins Constant blood level may be obtained Used for the administration of irritant or caustic drugs due to: Rapid dilution by the circulating blood Insensitivity of venous wall to pain Disadvantage Sudden excessive drug concentration at a target organ (drug shock) Once the dose is taken, anti-doting may be impossible Thrombosis is possible if extreme sites are used for injection E.g ankle, wrist or when the drug is potentially irritant Pharmaceutics III Page 9

10 IV infusion Term IV infusion is used for volume more than 10 ml. IV infusions administers a large volume of fluid at a slow rate and ensures that the drug enters the general circulation at a constant rate. The drug plasma rises soon after the start of infusion and achieves a steady state when rate of drug addition equals the rate of drug loss. Upon stopping infusion, elimination of the drug from the body by metabolism and /or excretion generally follow first order (proportional to the drug concentration) The term also available for Large volume parenteral (LVP) range ml. IV admixture IV combination for LVP prior or during administration (as a unit product) is known as IV admixture. Used to provide continuous or prolonged drug effect Specialized Routes Intra-arterial : direct injection into an artery (due to the fast flow of the blood in the artery, the drug will rapidly disperse throughout the blood system or to target the drug to a specific organ or tissue that is served by the artery) Intra-spinal: into spinal canal (aq. Solution injected in a volume less than 20 ml into a particular area of the spinal column) Intra-thecal: direct into cerebral spinal fluid Intra- articular: injection into a joint (aq. Solution or suspension) Intra cardial : direct injection into the heart ( aqueous solution applied in emergency) Intra-pleural: inject into the pleural cavity or a lung Pharmaceutics III Page 10

11 SPECIALIZED LVP AND STERILE SOLUTIONS Hyperalimentation: The administration of Nutrients and Vitamins by intravenous feeding, especially to individuals unable to take in food through the alimentary tract It is a medical procedure used for individuals who cannot get nutrients from food. This is done mainly due to impaired gastrointestinal (GI) conditions such as severe malabsorption, progressed eating disorders etc. Dialysis is a process for removing waste and excess water from the blood, and is used primarily as an artificial replacement for lost kidney function in people with renal failure. A- Peritoneal dialysis solution Sterile solutions injected (and continuously withdrawn) into the abdominal cavity for bathing the peritoneum for minutes Used: to rapid removal of drugs or chemical toxicity To counteract acute renal failure (toxic or metabolites diffuse into circulating fluids & removed) In peritoneal dialysis, a sterile solution containing glucose (called dialysate) is run through a tube into the peritoneal cavity, the abdominal body cavity around the intestine, where the peritoneal membrane acts as a partially permeable membrane. The peritoneal membrane or peritoneum is a layer of tissue containing blood vessels that lines and surrounds the peritoneal, or abdominal, cavity and the internal abdominal organs (stomach, Pharmaceutics III Page 11

12 Spleen, liver, and intestines). Diffusion and osmosis drive waste products and excess fluid through the peritoneum into the dialysate until the dialysate approaches equilibrium with the body's fluids. Then the dialysate is drained, discarded, and replaced with fresh dialysate. This exchange is repeated 4-5 times per day; automatic systems can run more frequent exchange cycles overnight. Peritoneal dialysis is less efficient than hemodialysis, but because it is carried out for a longer period of time the net effect in terms of removal of waste products and of salt and water are similar to hemodialysis. Peritoneal dialysis is carried out at home by the patient, often without help. This frees patients from the routine of having to go to a dialysis clinic on a fixed schedule multiple times per week. Peritoneal dialysis can be performed with little to no specialized equipment (other than bags of fresh dialysate). Ex: glucose solution containing the same ionic contents of the extra-cellular fluids Pharmaceutics III Page 12

13 B- Haemodialysis solution In hemodialysis, the patient's blood is pumped through the blood compartment of a dialyzer, exposing it to a partially permeable membrane. The dialyzer is composed of thousands of tiny synthetic hollow fibers. The fiber wall acts as the semipermeable membrane. Blood flows through the fibers, dialysis solution flows around the outside of the fibers, and water and wastes move between these two solutions. The cleansed blood is then returned via the circuit back to the body. Ultrafiltration occurs by increasing the hydrostatic pressure across the dialyzer membrane. This usually is done by applying a negative pressure to the dialysate compartment of the dialyzer. This pressure gradient causes water and dissolved solutes to move from blood to dialysate, and allows the removal of several litres of excess fluid during a typical 4-hour treatment. Pharmaceutics III Page 13

14 Is an electrolytes solution simulating body fluid and it is used for artificial kidney apparatus C- Irrigation solutions Used to irrigate and clean body cavities wounds. They must be sterile, pyrogen free Normal saline may be used as irrigative solution If designed (labeled) irrigative should not used as parenteral Injection Dosages Small volume parenterals - are sterile and Pyrogen free. - are packed in volume up to 100 ml. as:- Single- dose ampoules (glass thin walled containers made of type I borosilicate glass or may be plastic) Pharmaceutics III Page 14

15 Multiple- dose vials:- thick-walled glass & the container is sealed with rubber closure Prefilled syringes:- is aseptically filled into sterile syringes. The packed solution has a high level of sterility assurance & does not contain an antimicrobial preservatives. The product is available for immediate use. (use is limited because. It is expensive) Pharmaceutics III Page 15

16 ADDITIVES Substances added to the product to:- Provide efficacy Safe Elegant products Maintain pharmaceutical stability Ensure sterility Aid in parenteral administration Antioxidants Role of antioxidants An antioxidant is a molecule that inhibits the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent. Oxidation reactions can produce free radicals. In turn, these radicals can start a chain reaction. When the chain reaction occurs in a cell, it can cause damage or death to the cell. Antioxidants terminate these chain reactions by removing free radical intermediates, and inhibit other oxidation reactions. They do this by being oxidized themselves, so antioxidants are often reducing agents such as this, ascorbic acid, or polyphenols. To prevent degradation active ingredients and maintain product stability during shelflife. Pharmaceutics III Page 16

17 Stability of drugs that possess the low oxidation potential are susceptible to oxidative degradation. This can be prevented by applying different techniques:- The common antioxidant parenteral are: Sodium Bi-sulfite, Sodium meta- bisulfite Ascorbic acid Mechanisms of Action for aqueous They will preferentially oxidized instead of the drug or block oxidative chain reaction Displace the air by inert gas bubbled to solution prior to filling and sealing in the final products. Eg. N 2 and CO 2 Addition of free radical scavengers to block the oxidative chain reaction Eg. Vit. E and Vit. C Pharmaceutics III Page 17

18 Antimicrobial (preservatives): have a dual role A- In multiple dose: act as bacteriostatic 1- (inhibit the growth of any microbes accidentally introduced due to repeated doses 2- protect the product from minor contamination during formulation process Required for all multiple-dose products Not used for LVP (toxic effect) Added to the most unit-dose solutions that are terminally sterilized (Terminal sterilization is the process of sterilizing the final packaged product ) Preservative Should be compatible with the drug & excipients or injection components e.g containers & closures Effective in non-toxic concentration Effective after formulation and near the expiration date Antimicrobial test should be evaluate the antimicrobial activity of preservative in the final packaged product Buffers Added to resist ph changes during storage Requirements for ideal buffer Have adequate buffer capacity to maintain the ph of the product at stable value Ideal ph of parenteral product is ph 7.4 At ph above 9 lead to necrosis If below ph 3 pain in tissues Doesn't cause drug degradation Pharmaceutics III Page 18

19 E.g. Citrate buffer increase the degradation of Vit. B 12 Doesn't affect the isotonicity and stability of the product. ph of many official preparations is adjusted due to 1- To increase the stability of injection 2- minimize pain, irritation, necrosis 3- To provide unsuitable conditions for the growth of microorganisms 4- To enhance physiological activity, ph of product should be kept as physiologically possible with acceptance stability 5- control the drug solubility (as desired) 6- provide unsatisfactory conditions for growth of micro-organism (M.O cant resist low or high ph) 7- The ph of the product can be influenced by product degradation, container, stopper, diffusion of gases The product, is buffered to obtain maxm. solubility and resist change in ph. Buffers for parenteral use either weak acid and its salts or weak bases and its salts Sequestering agents (chelating agents) Used to complex or inactivate e.g metals copper, iron and zinc Metal contamination related to: raw materials, solvent e.g water Rubber stoppers and containers equipment ex. Of chelating agents: 1- Ethylenediamine tetra acetic acid (EDTA) 2- salts of citric and tartaric acid there activity increase in presence of reducing agents Pharmaceutics III Page 19

20 Inert gases Usually, Applied to enhance the integrity of oxygensensitive medications (increase stability) to replace oxygen the main cause of decomposition Ex: nitrogen and CO 2 For best results Use boiling water to remove air Purging the container with inert gases prior to filling Use glass-seal ampoules provide a barrier for gas transmission Use of butyl rubber stock better resistance to gas permeation than other rubbers Solubilizing agents and surfactants Solubilizing agents To increase drug solubility e.g lecithin, PEG, glycerol, ethyl alcohol (steroids, fatsoluble vit.) Surfactants SAA to increase dispersion of colloidal particles, increase powder wettability and prevent crystal growth for suspension & provide acceptable syringability. E.g Lecithin- Obtained from egg yolk, or soya beans sources. Osmotic pressure and tonicity adjustment agents Osmosis = passage of solvent molecules through semipermiable membrane from dilute to concentrated soln until equilibrium Osmotic pressure = force or pressure responsible for this process Iso-osmotic (isosmotic ) solutions = have the same osmotic pressure Pharmaceutics III Page 20

21 Iso-tonic solutions = solutions have the same osmotic pressure as body fluids (electrolytes concentrations) Hyper tonic solutions = solutions have higher O.P. than body fluids. Disadv. 1- allow water to move outwards from RBCs through their semipermeable membrane lead to shrink of cells (reversible mechanism) 2- Drain fluids extensively from body tissue and organs Ex: hypertonic solution used for: * NaCl solution used for abortion or emesis by local action * Wrong administration of large volume hypertonic normal saline may cause hemorrhage encephalopathy (drainage of brain fluids) and renal failure (kidney necrosis, and to pregnant females abortion. Hypo-tonic solutions = solutions have lower O.P. than body fluids. Disadv. 1- allow water to move into RBCs through their semipermeable membrane lead to swell rapidly and brust (haemolysis) of cells (irreversible mechanism) 2- not recommended in parenterals (can be adjusted by NacL, KCl, glucose, mannitol) Osmolarity of plasma = 306 milliosomole mosmol /liter Pharmaceutics III Page 21

22 Parenterals deviate from this value cause: Hemolysis of RBCs, Tissue irritation Pain on injection Shrinking of RBCs Large volume parenteral should be isotonic Small volume S.C, I.M, I.V may be hypertonic Large volume parenteral should be isotonic (have osmolarity ranging from mosmol/L) ex: glucose 5% infusion (= 280 mosmol/l) 0.9% Sod. Chloride (308 mosmol/l) Pharmaceutics III Page 22

23 Vehicle Aqueous Non aqueous Should be pharmacologically inert, non toxic, compatible with blood, maintain solubility of the drug Physically and chemically stable Unaffected by the ph changes. Not interfere with the therapeutic activity of injection Water Advantage Ideal for most injections Well tolerated Safest Easiest to administer Help to provide uniform dose More accurately measured Easy visual inspection for particulate contamination, chemical (ppt), color change Disadvantage May accelerate drug hydrolysis resulting in an inert or toxic products (powder for reconstitution) Not suitable for poorly soluble drugs Injection of distilled water may cause a rise in body temp. (pyrogenic = fever producing) Water free from this reaction = apyrogenic Pyrogen It is Lipid in nature and may be produced by many organisms, yeast, gram ve & gram +ve bacteria, fungi & viruses (non volatile) Non- microbial Pyrogens are :- some steroids & plasma components as they produce a pyrogenic response if injected Endotoxins isolated from the outer membrane of gram ve bacteria are composed of lipids that also produce Pharmaceutics III Page 23

24 significant physiological changes when injected (pyrogenic effect) They are fever-producing substances due to their toxic effect The most potent are associated with gram negative bacteria Source of pyrogen: solvent, medicament, additives, apparatus, containers Water is the greatest source of pyrogen in parenterals The contamination of LVP with pyrogen is serious, owing to the large volumes that are administered to seriously ill patients Types of water in pharmacy are 1- Purified water, USP is free of dissolved or solid impurities. is intended for use in the preparation of aqueous dosage forms, except those intended for parenteral administration (Injections) Should be freshly boiled and cooled immediately before use. Pharmaceutics III Page 24

25 2- Water for injection, USP: Used for parenteral solutions which are to be sterilized after their preparation. It is obtained by sterilizing pyrogen-free distilled water immediately after its collection. 3- Sterile water for injection, USP: water for injection which has been sterilized and packaged in single dose containers not greater than 1 liter size. it must be pyrogen-free not contain an antimicrobial agent or other added substance. This water is intended to be used as a solvent, vehicle, and diluent for alreadysterilized packaged injectable medications. The one-liter bottles not administered intravenously because they have no tonicity. used for reconstitution of multiple dose medication e.g antibiotics. In use, the water is aseptically added to the vial of medication to prepare the desired injection. 4- Bacteriostatic water for injection: sterile water for injection containing one or more suitable antimicrobial agents (to increase flexibility to multiple dose). The container label must state the name and proportion of the antimicrobial agent. Sterile vehicle in the preparation of small volumes of injectable preparations. Bacteriostatic agent gives the flexibility for multiple-dose vials. The preservative will destroy the contaminant microorganism Parenterals administered in large volumes is restricted due to excessive toxic amounts of antimicrobial agents that may be injected along with the medication. Generally, If volumes of greater than 5 ml of solvent are required, sterile water for injection rather than bacteriostatic water for injection is preferred. Pharmaceutics III Page 25

26 Sodium chloride injection, USP It is a sterile isotonic solution of sodium chloride (155 m Eq/L= ionic content of plasma) in water for injection. It contains no antimicrobial agents. used as a sterile vehicle in preparing solutions or suspensions of drugs for parenteral administration. Sodium chloride injection is frequently used as a catheter or IV infusion Ringer s injection, USP A sterile soln of NaCl, KCl, CaCl 2 (conc. similar to body fluids). Used as vehicle for drug or electrolytes replenisher Lactated ringer s injection, USP Lactated ringer s injection, USPA sterile soln of NaCl, KCl, CaCl 2 + sod. lactate Used as vehicle for drug or electrolytes replenisher Non- aqueous solutions If the drug is unstable in aqueous systems it may be necessary to use an alternative (nonaqueous solvent). To: 1- Increase drug stability 2-Improve solubility of poorly soluble drugs A-Water miscible non aqueous Ethyl alcohol (low conc to increase solubility) e.g dioxin and phenytoin injection BP Propylene glycol (PG) (non toxic, rapidly metabolized and excreted) Glycerol and polyethylene glycol (PEG) B-Water immiscible solvent Mainly used to dissolve drugs that are insoluble in water. Eg: steroids, hormones, vitamins Fixed oils of vegetable origin. 1- Almond Oil, (glycerides of oleic acid) used as a solvent for oily phenol injections, Pharmaceutics III Page 26

27 2- Olive oil, sesame oil, maize oil, cottonseed oil, Soya oil and castor oil are all suitable for parenteral use. N.B = mineral oils (paraffins) not used for parenteral (not metabolized) Dosage forms for parenteral use A- solution Drug+ preservative + water solution sterile microfilteration 0.22 µm filter for heat sensitive preparation For thermostable: terminally autoclavesterilized after filling (assure sterility and package) Parenteral Suspension Ready-to-use injection Reconstituted prior to administer May contain 0.5-5% solid (reach 30% with antibiotics) Particle size less than 5 µm Should have good syringeability and injectability Bacteriostatic sodium chloride injection, USP It is a sterile isotonic solution of sodium chloride (0.9%) in water for injection. It contains one or more antimicrobial agents. Not packed in container greater than 30 ml Should be labeled Not for use in new born (toxicity) Syringeability = handling characteristics of suspension while withdrawing it from container to a syringe + its clogging and foaming tendency Injectability = suspension characteristics during injection (required pressure for injection Thixotropy = Preparation that is solid in absence of shearing force become fluid if shaken- Pharmaceutics III Page 27

28 - the original structure is resumed after few mins. at rest Advantage Suitable for insoluble drugs Increased stability Possible depot action Disadvantage Difficult formulation and manufacturing Patient discomfort Difficult dose uniformity Needs more additives 1-Surfactant: needed for wetting hydrophobic drug and prevent crystal growth e.g : lecithin, polysorbate --tween 80, 60 2-Suspending agent: to control sedimentation rate ( viscosity ): gelatin, povidone, CMC To hold suspended particles enough time for accurate dose Prevent reformation of particle clumps 3- ph adjustment : citric acid, sod. citrate 4- Antioxidant: ascorbic acid, sod. Bi sulfite, or metabisulfite, sod. Formaldhyde, thiourea 5-Preservative: should be tested to determine the most effective conc. Preparation steps of Parenteral suspension Sterilization and milling of active ingredients Sterilization of vehicle Or Dissolve all soluble components and sterilize them by autoclave or sterile filtration Add previously sterilized powder to the sterile soln aseptically Aseptic wetting and dispersion of active ingredients Aseptic milling of bulk suspension Aseptic filling of the bulk suspension in suitable containers Pharmaceutics III Page 28

29 Methods for preparation of sterile drug powder Sterile re-crystalization Dissolve drug--- sterile by filtration (0.022 um) Sterile anti-solvent --- then added to drug solution to allow drug to crystallize in situ then filter aseptically Spray drying Spray the drug soln. into dry chamber to come in contact with hot sterile gas (air) Rapid evaporation leaving sterile uniform drug powder Adv. Suitable for heat sensitive drug powder Uniform particle size Low particulate contamination Low price and rapid process Lyophilization Separation of solid substance from solution by freezing. (Evaporate the solvent by sublimation) Adv. Suitable for heat and oxygen sensitive drug More rapid solubility (rapid re-constituation) Reduced contamination Disadv. Expensive Difficult to form crystalline powder Low solvent content Parenteral Emulsion Suitable for IV administration --- Dispersed droplets p.s = um --- Stablized by surfactants (lecithin, tween 80, gelatin, serum albumin and CMC) Application A source of calories and essential fatty acids Pharmaceutics III Page 29

30 Vehicle for drugs showing more stability, safety and efficacy in emulsion form. Ex: dexamethazone palmitate parenteral emulsion 5-6 active >>> its solution form Diazepam emulsion showed lower toxicity than solution. Physostigmine salicylate emulsion more stable than its soluton Disadv. of parenteral emulsion 1- Unstable product, difficult sterilization of the product (heat influence stability & impossible filtration) 2- rapid growth of M.O (not contain preservative) 3-difficult manufacturing steps under aseptic condition. 4- Unstable system upon storage (increase globule size--- cause thrombosis if injected IV) 5- Long term emulsion therapy may lead to overloading syndrome (fever, anemia, hepato-spleenomegaly. Dry powder Unstable drugs presented in form of dry pd for reconstitution prior to administration with vehicle. If solution will be the final dosage form should labeled for injection or sterile If suspension sterile for suspension Ex: sterile ampicillin trihydrate for suspension Containers and package of parenterals - Integral part of the product (bec. Stability, potency, safety) Should reject any component of packaging which is not safe, incompatible or affect stability) Pharmaceutics III Page 30

31 1- Glass containers: - multi-dose (vial) Single dose (Ampoule) Large volume parenteral L P (now used in plastic forms) Role of containers and closures that are used for packing of parenterals 1- maintain the sterility of the packed product 2- Withstand sterilization process 3- Allow withdrawal of the contents Materials of parenteral containers A- Glass 1- transparent and chemically inert, 2- excellent compatibility 3- Good product presentation, 4- good product identification colored glass used to resist deterioration of the product by light Carbon& sulfur, iron & manganese (Amber) Compd of cadmium and sulfur (yellow) Cobalt oxide or cupric oxide (blue) Iron oxide, manganese dioxide & chromium dioxide (Green) Types of glass 1- Type I Neural (neutral or borosilicate) 2- Type II (Soda glass with a surface treatment) 3- Type III (Soda glass of limited alkalinity) 4- NP glass ( Soda glass for non parenteral use) Glass bottle are normally made of glass type II Plastics containers 1- Poly vinyl chloride P C collapsible bags are used to package most infusion fluids. Pharmaceutics III Page 31

32 They are designed with port for the attachment of administration set and an additive port for addition of small-volume parenteral fluids. Resistant to impact Flexible and collapse during fluid administration & do not require an air inlet system. 2- Semi- rigid polyethylene containers :- These containers are intended for single use. Rubber Closure 1- saturated elastomers Copolymer of poly-isobutylene and polyisoprene Ethylene propylene rubber Ethylene propylene diene rubber Silicone rubber 2- Unsaturated elastomers Poly-isoprene Poly butadiene Styrene butadiene Poly-chloroprene Compatibility with the preparation Leaching form stopper is the most common leading to turbidity or precipitation Reaction with preparation Sorption of preservative or other ingredients Methods of evaluation: Microscopic examination of particulate matter Evaluation of solution by ultraviolet Infrared, thin layer chromatography,. Pharmaceutics III Page 32