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Sterile Dosage Forms

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Sterile Dosage Forms

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Sterile Dosage Forms

  1. 1. STERILE DOSAGE FORMS Dr. Basavaraj K. NanjwadeM. Pharm., Ph. D Department of Pharmaceutics Faculty of Pharmacy Omer Al-Mukhtar University Tobruk, Libya. E-mail: nanjwadebk@gmail.com 2014/06/10 1 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.
  2. 2. CONTENTS • Introduction • Routes of parenteral administration • Components of parenteral products • Antioxidants • Antibacterial • Buffers • Chelating agents • Inert gases • Surfactants • Solvents systems • Non-aqueous vehicles • Containers and closures • Formulation of parenterals (solution) • Suspensions • Emulsions • Dry powders • Sterilization • Radiopharmaceuticals • Radiation protection • Ophthalmic preparations • Packaging of ophthalmic products • References 2014/06/10 2 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.
  3. 3. Introduction • The human eye is a remarkable organ and the ability to see is one of our most treasured possessions. Thus the highest standards are necessary in the compounding of ophthalmic preparations and the greatest care is required in their use. It is necessary that all ophthalmic preparations are sterile and essentially free from forign particle. • Parenteral preparations are sterile preparations intended for administration by injection, infusion or implantation into the human or animal body. 2014/06/10 3 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.
  4. 4. Routes of parenteral administration • Intravenous injections and infusions • Subcutaneous injections • Intramuscular injections • Intradermal injections • Intra-arterial injections • Intracardic injections • Intraspinal injections • Intra-articular injections 2014/06/10 4 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.
  5. 5. 2014/06/10 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya. 5 Routes of parenteral administration
  6. 6. Components of parenteral products • Vehicles • Stabilizers • Buffering agents • Tonicity factors • Solubilizers • Wetting, suspending, emulsifying agents • Antimicrobial compounds 2014/06/10 6 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.
  7. 7. Antioxidants • Many drugs in aqueous solutions are easily degraded by oxidation. Small-volume parenteral products of these drugs often contain an antioxidant. • Bisulphites and metabisulphites are commonly used antioxidants in aqueous injections. • Antioxidants must be carefully selected for use in injections to avoid interaction with the drug. • Antioxidants have a lower oxidation potential than the drug and so are either preferentially oxidized or block oxidative chain reactions. 2014/06/10 7 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.
  8. 8. Antibacterial • Antibacterials may be divided into two groups according to their speed of action and residue production: • The first group contains those that act rapidly to destroy bacteria, but quickly disappear. E.g. alcohols, chlorine, peroxides, and aldehydes. • The second group consists mostly of newer compounds that leave long-acting residues on the surface to be disinfected and thus have a prolonged action. E.g. triclocarban, and benzalkonium chloride. 2014/06/10 8 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.
  9. 9. Buffers • The ideal pH of parenteral products is pH 7.4. • If the pH is above pH 9, tissue necrosis may result, whilst below pH 3 pain and phlebitis in tissues can occur. • Buffers are included in injections to maintain the pH of the packaged product. • pH changes can arise through interaction between the product and the container. • Acetate, citrate and phosphate buffers are commonly used in parenteral products. 2014/06/10 9 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.
  10. 10. Chelating agents • Chelating agents such as disodium edetate may be included to chelate the metal ions and thus enhance stability. • It is seen that disodium edetate is a very useful adjuvant to ophthalmic preparations at concentrations of up to 0.1 % w/v to enhance antibacterial activity and chemical stability. • It has also been used at higher concentrations as an eye drop for the treatment of lime burns in cattle. 2014/06/10 10 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.
  11. 11. Inert gases • An inert gas is  a  gas  which  does  not  undergo  chemical reactions under a set of given conditions.  • Inert  gases  are  used  generally  to  avoid  unwanted  chemical reactions degrading a sample.  • The  term inert gas is  context-dependent  because  nitrogen  gas  and  several  of  the  noble  gases  can  be  made to react under certain conditions. • Purified nitrogen and argon gases are most commonly  used as inert gases. 2014/06/10 11 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.
  12. 12. Surfactants • Certain  compounds,  because  of  their  chemical  structure,  have  a  tendency  to  accumulate  at  the  boundary  between  two  phases,  such  compounds  are  termed surfactants.  • The  adsorption  at  the  various  interfaces  between  solids,  liquids  and  gases  results  in  changes  in  the  nature  of  the  interface  which  are  of  considerable  importance in pharmacy.  • Surfactants  are  generally  classified  according  to  the  nature of the hydrophilic group. 2014/06/10 12 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.
  13. 13. 2014/06/10 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya. 13 Surfactants
  14. 14. Solvents systems • The drug is generally present in an injection in low  concentration.  • The  vehicle  provides  the  highest  proportion  of  the  formulation  and  should  not  be  toxic  nor  have  any  therapeutic activity. • The first choice of solvent is obviously water. • However, although the drug may be freely soluble, it  may be unstable in aqueous solution. 2014/06/10 14 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.
  15. 15. Non-aqueous vehicles • Water-miscible  co-solvents,  such  as  glycerin  and  propylene glycol are used as vehicle in small-volume  parenteral fluids. • They are used to increase the solubility of drugs and  to stabilize drugs degraded by hydrolysis. • Metabolizable oils are used to dissolve drugs that are  insoluble  in  water.  E.g.  Steroids,  hormones  and  vitamins are dissolved in vegetable oils.  • These formulations are administered by intramuscular  injection. 2014/06/10 15 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.
  16. 16. Large-volume parenteral fluids are packed into: • Glass bottles • PVC collapsible bags • Semi-rigid polythene containers The containers and closures that are used for packaging  parenteral products must; • Maintain the sterility of the packed fluids • Withstand sterilization • Be compatible with the packed fluid • Allow withdrawal of the contents 2014/06/10 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya. 16 Containers and closures
  17. 17. 2014/06/10 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya. 17 Containers and closures
  18. 18. Containers • Parenteral preparations are usually supplied in glass  ampoules, bottles or vials, plastic bottles or bags, and  prefilled syringes, which are coloured in the case of  light-sensitive substances. • Containers  should  be  made  from  material  that  is  sufficiently transparent to permit the visual inspection  of the contents.  • They  should  not  adversely  affect  the  quality  of  the  preparation, allow diffusion of any kind into or across  the material of the container. 2014/06/10 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya. 18
  19. 19. Closures • Closures for parenteral preparation containers should  be  equipped  with  a  firm  seal  to  prevent  entry  of  microorganisms and other contaminants. • They  should  not  be  made  of  components  that  react  with  the  contents,  nor  should  they  allow  foreign  substances to diffuse into the preparation.  • Plastic materials or elastomers of which the closure is  composed  should  be  sufficiently  firm  and  elastic  to  allow the passage of a needle with the least possible  shedding of particles.   2014/06/10 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya. 19
  20. 20. 2014/06/10 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya. 20 Containers and closures
  21. 21. Formulation of parenterals (solution) • Aqueous solutions – High viscosity solutions • For compound with mol. wt. more than 750 • For water solution drugs • Gelling agents or viscosity enhancers are used – Complex formulations • Drug forms dissociable complex with macromolecule • Fixed amount of drug gets complexed • Given by I.M. route 2014/06/10 21 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.
  22. 22. • Oil solutions – Drug release is controlled by controlling partitioning of drug out of oil into surrounding into aqueous medium – For I.M. administration only – No. of oils are limited • LVP usually contains one or more electrolytes – Potassium chloride is the most common additive – Other salts of potassium, magnesium, or sodium can be added • Additives to I. V. solutions can also be multivitamins or trace elements Formulation of parenterals (solution) 2014/06/10 22 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.
  23. 23. Solution • The vehicles most commonly used for IV infusions are: – Dextrose in water – NS solution – Dextrose in saline solution • The two main types of IV solutions are: – small-volume parenterals (SVPs) of 50 or 100 mL – large-volume parenterals (LVPs) of more than 100 mL 2014/06/10 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya. 23
  24. 24. Suspension • Suspension for injection contain less than 5% of drug solids with a mean particle diameter within the range 5-10µm. • During the manufacture of suspension for injection, the components are prepared and sterilized separately, then aseptically combined. • The final product cannot be filter sterilized owing to the presence of particles in the formulation. • Powders for use in sterile suspensions can be sterilized by gas residues must be avoided. 2014/06/10 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya. 24
  25. 25. Suspensions • Aqueous suspensions – Given by I.M. or S.C. routes – Concentration of solids should be 0.5 to 5 % – Particle size should be < 10 μm – Drug is continuously dissolving to replenish the lost. – For oil soluble drugs – Only crystalline and stable polymorphic drugs are given by this form – Viscosity builders can be used. – E.g., Crystalline zinc insulin 2014/06/10 25 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.
  26. 26. • Oil suspensions – Given by I.M. route. – Process of drug availability consists of dissolution of drug particles followed by partitioning of drug from oil solution to aqueous medium. – More prolong dug action as compared to oil solution and aqueous suspension. – E.g., Penicillin G procaine in vegetable oil Suspensions 2014/06/10 26 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.
  27. 27. Emulsions • Can be given by I.M., S.C., or I.V. routes • O/w systems are not used due to large interfacial area and rapid partitioning. • W/o emulsions are used for water soluble drugs. • Multiple emulsions are used generally such as w/o/w and o/w/o since an additional reservoir is presented to the drug for partitioning which can effectively retard its release rate. 2014/06/10 27 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.
  28. 28. Emulsions • Release of water soluble drugs can be retarded by presenting it as oil suspension and vice versa. Aqueous phase Oil phase Water soluble drug e.g., 5-Fluorouracil Oil soluble drug e.g., lipidol 2014/06/10 28 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.
  29. 29. Dry powders • Dry sterile powder is aseptically added to a sterile vial. • The dry drug powder is reconstituted with a sterile vehicle before use. • Powders for injections are solid substances, distributed in their final containers and which, when shaken with the prescribed volume of the appropriate sterile liquid, rapidly form either clear and practically particle-free solutions or uniform suspensions. 2014/06/10 29 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.
  30. 30. Sterilization • Products to a process to a process whereby all viable life forms are either killed or removed. • The sterilization process is usually the final stage in the preparation of the product. • The methods of sterilization in regular use include exposure to: saturated steam under pressure, dry heat, ionizing radiation, ethylene oxide or passage through a bacteria retaining filter. • When possible, exposure to saturated steam under pressure is the sterilization method of choice. 2014/06/10 30 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.
  31. 31. Radiopharmaceuticals • Radiopharmacy is concerned with the manufacture of radioactive medicines known as radiopharmaceuticals. • These have two main applications in medicine: 1. As an aid to the diagnosis of disease (diagnostic radiopharmaceuticals) 2. In the treatment of disease (therapeutic radiopharmaceuticals) 2014/06/10 31 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.
  32. 32. • Diagnostic radiopharmaceuticals may be classified into two types: 1. Radiopharmaceuticals used in tracer techniques for measuring physiological parameters (e.g. 51 Cr-EDTA [Ethylenediaminetetraacetic acid] for measuring glomerular filtration rate) 2. Radiopharmaceuticals for diagnostic imaging (e.g. 99m Tc-methylene diphosphonate (MDP) used in bone scanning). 2014/06/10 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya. 32 Radiopharmaceuticals
  33. 33. Radiation protection • There are three basic principles to radiation protection: 1. Shielding: By placing shielding around the radioactive source the radiation dose rate may be reduced. 2. Distance: The radiation dose from a radioactive course is inversely proportional to the square of the distance. 3. Time: Minimizing the time spent handling a radioactive source will reduce the radiation dose. 2014/06/10 33 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.
  34. 34. Ophthalmic preparations • Eye drops • Eye lotions • Eye ointments • Ophthalmic inserts • Contact lenses and their solutions • Solutions • Suspensions • Emulsions • Ointment • Gels • Erodible inserts • Non-erodible inserts 2014/06/10 34 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.
  35. 35. • Eye drops including solutions and suspensions of active medicaments for instillation into the conjunctival sac. • Eye lotions for irrigating and cleansing the eye surface, or for impregnating eye dressings. • Eye ointments, creams and gels containing active ingredients for application to the lid margins and/or conjunctival sac. • Contact lens solutions to facilitate the wearing and care of contact lenses. • Parenteral products for intracorneal, intravitreous or retrobulbar injection • Ophthalmic inserts placed in the conjunctival sac and designed to release active ingredient over a prolonged period 2014/06/10 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya. 35 Ophthalmic preparations
  36. 36. Packaging of ophthalmic products • Contact lens solutions are usually packed in plastic containers. • It is imperative that the low concentrations of antimicrobials present in these products are not reduced to ineffective levels due to sorption effects with the plastic. • Contact lens storage cases are also of importance to the contact lens wearer. • It is important that these containers are kept in a hygienic conditions. 2014/06/10 36 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.
  37. 37. THANK YOUe-mail: nanjwadebk@gmail.com 2014/06/10 37 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.

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