Quality control of parentral products, suspensions and emulsons

Quality control of parentral products

• Quality control of parentral products• Injections are sterile, pyrogen free preparations

intended to be administered parenterally (outside alimentary tract).

• All parenterals, as well as nasal, ophthalmic solutions, must be sterile, including packaging materials.

• Containers for parenteral preparations are made as far as possible from materials that are sufficiently transparent to permit the visual inspection of the contents, except for implants

• Parenteral preparations are supplied in glass containers or in other containers such as plastic containers and prefilled syringes.

• The tightness of the container is ensured by suitable means. Closures ensure a good seal, prevent the access of microorganisms

and other contaminants and usually permit the withdrawal of a part or the whole of the

contents without removal of the closure.

• Contamination:• Chemical composition• –pH• –Sterility (e.g.microorganism contamination)• –Pyrogenicity• –Physical appearance• –Particulate matter (e.g. dust, glass or precipitation)

• Sources of product contamination• – Touch contamination• – Generation of particulates from shedding cells or hair• ● Air Supply• – Heating, Ventilation and Air Conditioning (HVAC)• ● Infiltration• – Particles from adjacent spaces (e.g. entrance, hall)• ● Internal generation• – Walls, floors, ceilings, packaging, equipment

• Necessities of Parenteral preparations:• –Sterility (must)• –Free from Pyrogen (must)• –Free from particulate matter (must)• –Clarity (must)• –Stability (must)• –Isotonicity (should)• –Solvents or vehicles used must meet special purity and other• standards.• –Restrictions on buffers, stabilizers, antimicrobial preservative.• Do not use coloring agents.• –Must be prepared under aseptic conditions.• –Specific and high quality packaging.

● Parenteral products require additional tests, which include those of sterility, pyrogen, clarity, and particulate analysis, and for glass-sealed ampoules, leaker test.

• 1.Volume in container• ● The total fluid volume that must be filled into a unit

parenteralcontainer is typically greater than the volume that would contain the exact labeled dose.

• 2. Clarity testing and particulate analysis:• a. Clarity examination• b. Particulate matter

• 3. Pyrogen test: Pyrogenic substances are primarily lipid polysaccharide products of the metabolism of microorganisms, they may be soluble, insoluble or colloidal.

• Pyrogen produced by gram-negative bacilli are generally the most potent. Minute amounts of pyrogens produce a wide variety of reactions

in both animals and humans, including fever, leukopenia and i.e alteration in blood coagulation.

• One pyrogen test is a qualitative biological test based on the fever response of rabbits. The test aims of measuring the rise in body temperature in healthy rabbits by the intravenous injection of a sterile solution of the substance under test.

• Sources of pyrogen contamination• - Solvent-possibly the most important source.• - The medicament• - The apparatus• - The method of storage between preparation and

sterilization

• Rabbit pyrogen test• ● Rabbits must be healthy and mature• ● Either sex may be used• ● Must be individually housed between 20 and 23°C• ● Weighing not less than 1.5 kg• ● Fed a complete and balanced diet not containing

antibiotics,• and not showing loss of body mass during the week

preceding• the test.

• Limulus Amoebocyte Lysate (LAL) test.• This test is more sensitive, more rapid, and

easier to perform than the rabbit test.

Quality control tests for Emulsions

• An emulsion is a biphasic liquid penetration containing two immiscible liquids, one of which is dispersed as minute globules into the other.

• Evaluation tests for emulsion Average globular size and size distribution Number of globules Rheological evaluation Zeta potential In vitro drug release In vitro stability study

• Determination of particle size and particle count: • -It is performed by optical microscopy and Coulter

Counter • Determination of viscosity: • -Determination of viscosity is done to assess the

changes that might take place during aging.

• The viscometers used: cone and plate viscometers.• In case of o/w emulsions, flocculation of globules

causes an immediate increase in viscosity. After this change, the consistency of the emulsion changes with time.

• In case of w/o emulsions, the dispersed phase particles flocculate quite rapidly resulting in a decrease in viscosity, which stabilizes after 5 to 15 days.

• As a rule, a decrease in viscosity with age reflects an increase of particle size due to coalescence.

• 3. Determination of phase separation:

• Phase separation may be observed visually or by measuring the volume of the separated phases.

• Determination of electrophoretic properties:• Determination of electrophoretic properties like zeta

potential is useful for assessing flocculation since electrical charges on particles influence the rate of flocculation.

• Assessment of emulsion shelf life:

• The final acceptance of an emulsion depends on stability, appearance, and functionality of the packaged product. Stress conditions employed for evaluating the stability of emulsions:

1. Aging and temperature

It is routine to determine the shelf life of all types of preparations by storing them for varying periods of time at temperatures that are higher than those normally encountered.

At elevated temperature: accelerates the rate of coalescence and creaming and this is coupled with change in viscosity. Most emulsions become thinner at elevated temperature and thicken when allowed to come to room temperature.

• Freezing damage emulsion more than heating

Since, the solubility of emulsifiers is more sensitive to freezing than heating.

Centrifugation

It is accepted that shelf life under normal storage conditions can be predicted rapidly by observing the separation of the dispersed phase due to either creaming or coalescence when emulsion is exposed to centrifugation.

Quality control of suspension

A pharmaceutical suspension is a coarse dispersion in which internal phase is dispersed uniformly throughout the external phase.

Rheologic methods: Viscosity of suspensions is of great importance for stability and pourability of suspensions. As we know suspensions have least physical stability amongst all dosage forms due to sedimentation and cake formation.

The viscosity of the dispersion medium increases, the terminal settling velocity decreases thus the dispersed phase settle at a slower rate and they remain dispersed for longer time yielding higher stability to the suspension.

On the other hand as the viscosity of the suspension increases, it’s pourability decreases and inconvenience to the patients for dosing increases.

A practical rheological method involves the use of Brookfield viscometer

• Electrokinetic techniques Such instrumentation permitted measurement of the

migration velocity of the particles with respect to the surface electric charge or the familiar zeta potential.

The evaluation of suspensions by electrokinetic methods showed that the zeta potential changes upon the addition of additives and is related to stability.

The zeta potential was correlated to visually observed caking

• Particle size changes • It used for stability testing purposes

Packaging and Storage of Suspensions: Should be packaged in wide mouth containers having

adequate air space above the liquid. Should be stored in tight containers protected from: • freezing. • excessive heat & light.• Label: "Shake Before Use" to ensure uniform

distribution of solid particles and thereby uniform and proper dosage.