Large volume parentrals and small volume parentrals (Lvps and Svps)

Defination of Lvps and Svps
Formulation of Lvps and Svps
Evaluation

1. Rajiv Gandhi University of health and science Bangalore Large and small volume parentrals

2. Content Introduction General requirement for parenteral dosage form Parenteral Routes Advantages and Disadvantage Classification Small volume parenterals (SVPs) Large volume parenterals (LVPs)

3. Introduction The term derived from Greek word ‘Para’ outside & ‘ Enterone ’ intestine. Parenterals are sterile solutions or suspension of drug in aqueous or oily vehicle Parenteral drugs are administered directly in to the veins, muscles or under the skin, or more specialized tissues such as spinal cord. Term parenteral used for any drug/fluid whose delivery doesn’t utilize the alimentary canal for entering in to the body tissues.

4. General requirements for parentrals dosage form Stability Sterility Free from pyrogens & toxins Free from foreign particles Isotonic Chemical purity

5. Parentrals routes The term parenteral literally means to avoid the gut (gastrointestinal tract) and refers to any route of administration outside of or beside the alimentary tract. Thus, parenteral are injectable drugs that enter the body directly and are not required to be absorbed in the gastrointestinal tract before they show their effect. Parenteral routes of administration usually have a more rapid onset of action than other routes of administration. 1. Intravenous 2. Intramuscular 3. Subcutaneous 4. Intradermal 5. Intrathecal 6. Intraarterial

6. Advantages Rapid onset of action . Useful for emergency situation. Avoid first pass metabolism. Complete bioavailability. Useful for patients who cannot take drugs orally

7. Disadvantages Painon injection. Trained person is required. Difficult to reserve an an administered drugs effects.  Sensitivity or allergic reaction at the site of injection. Requires strict control of sterility. Require specialized equipment, device.

8. Classification Based on volume Small volume parenterals (SVPs) Large volume parenterals (LVPs)

9. Difference between LVP and SVP Small Volume parenteral Volume- upto 100 ml Route – any other parenteral route Containers- small glass containers like ampoules and vials Use –multiple dose Example- Drugs in solution, emulsion and suspension Large volume parenterals Volume- More than 100ml Route- only by IV Container- Large glass/plastic containers of capacity upto 1lit Use –single dose Example- Saline solution (NS)

10. Small volume parenterals (SVPs) The volume is generally less than or equal to 100ml. They are supplied in single or multiple dose. They are used to dispense most of the drugs. Examples: Ampoules and vials Types of Small volume parenterals 1. Solution 2. Suspensions 3. Emulsions 4. Dry Powder

11. Large volume parenterals (LVPs) These are supplied for single dose having more than 100ml. These are delivered through IV route. These generally provides electrolyte, nutrition to the body Example Normal saline. Types of LVPs 1. Hyper alimentation solution 2. Cardiolplegic solution 3. Peritoneal dialysis solution 4. Irrigating solution

12. HyperalimentationSolutions Administration of large amtof nutrients to patients who unable to take food orally. Formulation: Mix of dextrose,aminoacids , lipids, electrolytsand vitamins.TotalParenteral Nutrition

13. Cardioplegic solutions LVPs are used in heart surgery to prevent injury to myocardium during reperfusion,as well as to maintain bloodless operating field. Maintain the diastolic arrest. Administered in cold form. Slightly alkaline to compensate metabolic acidosis. Hypertonic Use To minimize reperfusion injury resulting from tissue edema

14. Peritoneal dialysis solution Infused continuously into abdominal cavity,bathing peritoneum & are then continuously withdrawn. Use 1. Removal of toxic substances from body 2. To aid and accelerate excretion normal. 3. To treat acute renal insufficiency.

15. Irrigating Solutions To irrigate,flush,and aid in cleaning body activities and wounds. Certain IV solutions (normal saline) may be used as irritating solution, but solution designed as irritating solution should not be used parentrally . Use Treatment of serious wounds infused in to blood stream.

16. Formulation aspects Therapeutic agents. Ex: Insulin, Antibiotics, Vaccines, Antipyretics, Analgesics, Dextrose, Nacl , Electrolytes. • Vehicles. 1) Water. ■WFI, BWFI, SWFI. 2) Aqueous vehicles. “E.g.: Ethyl alcohol, Propylene Glycol. 3) Non-aqueous vehicles. E.g : Fixed oils (corn oil, peanut oil, cotton seed oil.)

17. Other Additives Antimicrobial agent Ex phenol and cresol,Phenyl mercuric nitrate and thiomersol . Buffers Ex Sodium bezoate and benzoic acid Antioxidants Ex Reducing agent-Ascorbic acid,Thiourea . Blocking agent- Tocophenol , Phosphate buffer . Synergists-Ascorbic acid,Tartaric acid . Chelating agent-EDTA Stabilizers Ex Glycerine, Sodium saccharine Surfactants Ex Lecithin, Propylene glycol

18. 6. Tonicity Adjuster Ex Glycerine,Lactose , Mannitol 7. Chelating agents Ex Tetrasodium edetate , Ethylene diamine tetraacetic acid 8. Co solvents Ex Alcohol 9. Bulking agent Ex Mannitol, Lactose, Sucrose, Dextran 10. Suspending agent Ex CMC,Methyl cellulose, Gelatin , Sorbitol 11. Emulsifying agents Ex Lecithin,Polysorbate 80,Gelatin

19. Physiological Consideration Requirements for parenteral preparation Sterile Apyrogenic Pure Stable Isohydric Isotonic The most convenient and simplest form of an parenteral product is an isotonic aq. Solution which have the pH close to that of blood and body tissues i.e pH 7.4 Aqueous solution which given through IM the release of drug may be controlled by- Increasing the vehicle viscosity by using MC,CMC or PVP and thus decreasing the molecular diffusion and localising injected drug.

20. pH consideration To adjust the pH to the physiological one (mineral or organic acids or salts) are used. The generation of pH/stability is the main step in the selection of pH in a formulation. Tolerability of formulation depends on its buffering capacity. Tonicity Consideration * An isotonic solution is one that exhibit the same effective osmotic pressure as blood serum. • To make the preparation isotonic with respect to blood (Glucose, Mannitol) are used. • For LVPs isotonicity is very essential. • To avoid the tissue damage parenteral formulation should be isotonic with human plasma.

21. Formulation consideration Choice of excipients In pharmaceutical products the formulation should developed by using excipients. In parenteral products the quality, particularly in microbial terms of excipients should be considered. The excipients have pharmacopoeial grade. Excipients are important to assure safety to minimise pain and irritation on injection and to control or prolonged drug delivery.  Pharmacokinetic of drug Pharmaceutics also affects the drug dose and the dosage regimen. A drug having a rapid pharmaceutic profile there is a need of development of modified release dosage formulation

22. Absorption rate is depend on type of formulation. Distribution, metabolism and excretion of drug have effect on route of administration.  Drug solubility . The formulation must contain a co-solvent for maintain drug in solution,if the drug is insufficiently soluble in water. . Solubility is the major factor that gives the concentration in the dosage form. A dispersed system dosage form developed when simple formulation additives do not result in the solution.  Drug stability If the drug possesses significant degradation problems in the solution,then sterile solid dosage form should be developed.

23. Sometimes drug concentration affects the stability, affects size and the packaging system used also. Stability determines the storage condition since it indicates the drug expiration date.

24. Manufacturing Manufacturing process (Based on the requirements of sterility) Production of parenterals 1. Cleaning 2. Preparation of bulk production 3. Filtration 4. Filling of solution in ampoules or vials 5. Sealing 6. Sterilization and quality control test

25. Filtration If product is a solution,after its compounding it should filter This process employed for clarify solution and removing particulate matter. It is accomplished by cold sterilization. Types :- Screening / Sieving- Entrapment or Impaction- Electrostatic attraction Membrane filters are used for parenteral preparation because they have high effective in particle retention,non -shedding property,non reactivity and have disposal characteristics.

26. Filling The solution which sterilized through filtration are to be filled under the aseptic condition. Filling is important for the prevention of contamination. Aseptic fill and by using media fills it is validated. The liquid is more easily exposed uniformly into the container. Liquid are easier to transfer than the viscous or sticky fluids. Filling types of liquid 1. Volumetric filling 2. Time/pressure filling 3. Netweight filling

27. Sealing The filled containers should be sealed as soon as possible to prevent contamination.It represents the final aseptic procedure. Ampoules : Sealing of ampoules are done by melting of the portion of the neck. Methods 1. Pull seals method 2. Tip seals Vials and Bottles : By closing the opening using the rubber closure (stopper) the glass or the plastic vials are sealed properly.

28. Sterilization Sterilization of parenteral products should be done after sealing to the final container that is called as terminal sterilization. 1.Heat sterilization *Moist heat *Dry heat –Hot air oven-Incineration 2.Filtration sterilization 3.Radiation *Non-ionizing radiation *Ionization radiation 4.Gaseous Sterilization

29. Packaging of parenterals Packaging of parenterals are done by A. Glass containers Type-I: Highly Resistant Borosilicate Glass Type II: Treated Soda lime Glass Type III: Regular Soda Lime Glass. Type IV: N.P (Non-parenteral) Glass Type 4 is not used for parenteral packaging, others all are used for parenteral packaging.

30. Plastic Plastic containers are used but they face following problems Permeation Sorption Leaching Softening 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 hysical instability

31. Evaluation of parenterals Sterility test method Membrane filtration method method Direct inoculation method Clarity test Leaker test Pyrogen test Types a.Rabbit test b.Limulus amebocyte lysate (LAL) test