Title 17. STERILE FORMULATIONS – LARGE AND SMALL VOLUME PARENTERALS.pdf ✅

PHARMD GURU Page 1 STERILE FORMULATIONS – LARGE AND SMALL VOLUME PARENTERALS PARENTERALS:  Parenterals are those pharmaceutical products that are given by other than oral route. TYPES OF PARENTERALS: Parenterals are mainly classified into two types. They are: 1. Small volume parenterals and 2. Large volume parenterals. SMALL VOLUME PARENTERALS:  An injection that is packed in a container and labeled as containing 100ml or less is known as small volume parenterals.  All the sterile products packed in vials, ampoules, cartridges, syringes, bottles or any other container that is 100ml or less, fall under the class of small volume parenterals.  Ophthalmic products packed in squeezable plastic containers, although topically applied to the eye rather than administered by injection, also fall under the classification of small volume injections as long as the container size is 100ml or less.  Small volume parenteral aqueous solutions can be administered by intravenous route because of local irritation.  Small volume parenteral products can be formulated and packed in several ways and include a wide variety of products like: a) Pharmaceutical products. b) Biological products. c) Allergic products. d) Radiopharmaceutical products. MANUFACTURE OF PHARMACEUTICAL PREPARATIONS
PHARMD GURU Page 2 e) Genetically engineered or biotechnology products. f) Liposome and lipid products. ADVANTAGES:  Can be given to the patients who cannot take drugs orally.  Raid onset of action.  Can be given in emergency situations.  First pass metabolism can be avoided.  Degradation of drug due enzymes can be prevented.  Drug can be directly injected into the target tissue.  Can be given to unconscious patients.  Drug action can be prolonged by modifying the formulation.  Transfusion fluids containing nutrients like glucose and electrolytes such as sodium chloride can be given by this route. DISADVANTAGES:  Pain and tissue damage at the site of injection.  Requires trained persons to administer the drugs.  Administration of the drug through wrong route can even cause death.  Difficult to save the patient when overdose is given.  Hypersensitivity reactions.  Expensive and costly.  Requires special equipment’s, devises and technologies to prepare and administer the drugs.  Requires strict control sterility and non-pyrogenicity than other formulations. FORMULATION OF SMALL VOLUME PARENTERALS: Requirements: In the preparation of parenteral products, the following substances are added to make a stable preparation:
PHARMD GURU Page 3 1. VEHICLES:  There are two types of vehicles which are commonly used for the preparations of injections: a) Aqueous vehicles:  Water is used as vehicle for majority of injections because water is tolerated well by the body and is safest to administer.  The aqueous vehicles used are: 1) Water for injection. 2) Water for injection free from CO2. 3) Water for injection free from dissolved air. b) Non-aqueous vehicles:  Commonly used non-aqueous vehicles are oils and alcohols.  Fixed oils such as arachis oil, cotton-seed oil, almond oil and sesame oil are used as vehicles.  Ethyl alcohol is most commonly used as vehicle. 2. ADJUVANTS: The following adjuvants are commonly used in preparing the stable parenteral preparations: i. Solubilizing agents. ii. Stabilizers. iii. Buffering agents. iv. Antibacterial agents. v. Chelating agents. vi. Suspending, emulsifying and wetting agents. vii. Tonicity factors.
PHARMD GURU Page 4 PROCEDURE: Cleaning of the glassware Weighing the required quantities Mix them with suitable vehicle Filter the resultant solution through 0.45 microns filter Filling Packing Manufacturing of parenterals are carried out under specially designed clean environment which is classified into: 1) Class 100:  It is defined as a room in which the particulate count in air is less than 100 per feet3 of 0.5 or longer in size. 2) Class 10,000:  It is defined as a room in which the particulate count in air is less than 10,000 per feet3 of 0.5 or longer in size. 3) Class 1,00,000:  It is defined as a room in which the particulate count in air is less than 1, 00,000 per feet3 of 0.5 or longer in size. AREAS: a) Cleaning area (white zone):  All the glassware and other equipment are cleaned in this area.
PHARMD GURU Page 5  Cleaning follows a specific rinsing cycle where the containers are placed under laminar air flow hoods and thoroughly cleaned using 3 different types of water.  Preliminary rinsing is carried out by distilled water followed by purified water and final rinsing with water for injection.  After rinsing the containers are dried using suitable drying procedures. b) Preparation area (black zone):  Required quantities of raw materials are weighed and transferred into mixing tanks, required volume of solvent is added and the mixture is stirred until all the solutes dissolve completely.  The formed solution is filtered through 0.45 micron filter to remove undissolved or particulate matter. c) Aseptic or filling area (red zone):  In this area filling is carried out under aseptic conditions.  The filled containers are transferred to quarantine area for sterilization process. d) Quarantine area(yellow zone):  The filled ampoules or vials are stored in this area during quality control check for various parameters. e) Packing and finishing area (green zone):  The filled containers are suitably labeled and transferred to secondary packing machines where the containers are suitably packed. Example: Preparation of ascorbic acid: 2/3rd of total volume of water is placed in a beaker Ascorbic acid is weighed and suspended in water with continuous stirring Sodium bicarbonate is slowly added with vigorous stirring, effervescence is produced After subsiding the effervescence, remaining sodium bicarbonate is added