Parenterals & Sterilization + Ophthalmic Dosage Forms

Parenteral preparations or Injectables

Sterile solutions or suspensions of drugs in aqueous or oily vehicle meant for administration into the body by means of injection under or through one or more layers of the skin or mucous membrane.

classification of parenteral products is based on the types of packaging, what are the various types?

• single dose units

• multiple dose units

Single dose units examples

Ampoules, infusions and prefilled disposable syringes

Multiple dose units examples

Multiple dose vials

Small volume parenterals

Volume varies from fraction of milliliters to 100 ml or less

Large volume parenterals

Volume varies from 100 ml to 1000 ml

Small volume parenterals examples

Furosemide, heparin, cimetidine and iron dextran injections.

Large volume parenterals examples

Infusion fluids, TPN solutions, patient controlled analgesic and dialysis fluid.

Based on Clinical Use

• Solutions for irrigation
• Dialysis solution
• Diagnostic agent
• Allergenic extracts
• Implants

Based on physical state of the product

• Sterile solutions
• Sterile suspensions
• Sterile emulsions
• Sterile solids

Small Volume Parenterals (SVPs)

A parenteral preparation sealed in a container of 100 ml or less volume

• Requires little or no manipulation
• Extended stability
• Little wastage
• Does not offer flexibility in quantity/concentration

Primary uses: Small Volume Parenterals (SVP)

• Therapeutic injections
• Ophthalmic products
• Diagnostic agents

Large Volume Parenterals (LVPs)

A preparation intended for IV infusion and sealed in a container of greater than 100 ml
volume

• Flexible but requires manipulation
• Used for maintenance or replacement therapy
• Free of preservatives

Clinical uses of Large Volume Parenterals (LVPs)

• Basic nutrition
• Restoration of electrolyte balance
• Fluid replacement
• Blood and blood products

Injection

Liquid preparations that are drug substances or solutions e.g. Insulin Injection, USP

For Injection Suspension

Dry solid that upon addition of suitable vehicles, yields solutions conforming in all respects to requirements for injections

e.g. Cefuroxime for injection, USP

Injectable Emulsion

Liquid preparation of drug substance dissolved or dispersed in a suitable emulsion medium

e.g. Propofol, USP

Injectable Suspension

Liquid preparation of solid suspended in a suitable liquid medium,

e.g. Methylprednisolone acetate suspension, USP

Used for Injectable Suspension

Dry solid that upon addition of vehicle yields preparations conforming to requirements for injectable suspension

e.g. Imipenem and Cilastatin. Official Types of Injections (USP)

Aqueous vehicles for injections

• Water for injection, USP
• Sterile water for injection, USP
• Sodium chloride injection, USP

Non-aqueous vehicles for injections

• Fixed vegetable oils
• Glycerin
• Polyethylene glycols
• Propylene glycols
• Alcohol
• Ethyl oleate
• Isopropyl myristate

Formulation of parenterals: Excipients

• Antimicrobials
• Buffers
• Antioxidants
• Tonicity agents
• Suspending agents
• Emulsifying agents

Ophthalmic dosage forms

Dosage forms used in the treatment of eye diseases

Ophthalmic dosage forms must be ____

sterile, particle free (some exceptions), isotonic and free from pyrogens/endotoxins

How are ophthalmic dosage forms prepared?

using aseptic techniques + procedures used to maintain the Sterility of the product

Ophthalmic Preparations

Specialized dosage forms designed to be administered on to:
• The external surface of the eye (topical)
• Inserted (intraocular) or
• Adjacent (periocular) to the eye in conjunction with an ophthalmic device

Intraocular & periocular preparations are restricted to _____ due to dangers associated with their administration, or repetitive administration

therapeutic applications or surgical adjuncts

Topical therapeutic ophthalmic dosage forms- examples

• Solutions
• Suspensions and ointments
• Gels and ocular inserts

Ophthalmic preparations are similar to parenteral dosage forms in their requirements for:

• Sterility
• Osmotic pressure (tonicity)
• Preservation
• Tissue compatibility
• Avoidance of pyrogens
• Particulate matter and suitable packaging

Normal fluid volume capacity of the eye is

~ 30 μl

Normal commercial eyedropper dispense ___

50-75 μl

higher drug contact time with the eye favors __ bioavailability

higher

In humans the normal turnover of tear fluids in the eye is every 2-3 minutes, which accounts for

the loss of drugs delivered ophthalmically

About half of the delivered ophthalmic dose is lost via

overflow

Sterility

Must be sterile to protect the eyes from infection

pH

pH 7.4 is ideal but the outer surface of the eye can tolerate a pH range of 6.5 – 8.

extreme pH causes ___ to the eye

irritation

viscosity

To increase the retention of the drug in the eye

Contact time

increased contact time achieved by increasing the viscosity of the formulation

Types of ophthalmic dosage forms: Solutions

Most commonly administered ocular dosage form

Examples of ophthalmic solutions

simple solutions, powders for reconstitution

solutions easily wash off from the eye, hence ____ contact time with the eye

less

Gel-forming solutions have ____ contact time with the eye

increased

Types of ophthalmic dosage forms: Suspensions

▪ Particle size must be less than 10 μm
▪ Particles should not aggregate into larger particles
▪ Polymorphism (due to storage temp, change in pH)

Ointments do not wash off easy, hence ____ duration of action

longer

Ointments have relatively ___ onset time and ___ time for peak drug absorption

slower; longer

Types of ophthalmic dosage forms: Drug-impregnated inserts

Provide drug release for extended period of time; sterile, thin, solid or semi-solid polymeric devices placed into the conjunctival sac or lower/upper fornix of the eye to deliver medication at a steady rate

Ocusert – Glaucoma therapy

▪ Release of pilocarpine at a fixed rate
▪ Eliminates need for frequent doses
▪ Placed in the cul-de-sac of the eye

What is an ocusert (ocular insert)?

a small, thin, and flexible wafer or disc placed inside the eyelid to release medication into the eye at a slow, constant rate

Identify the solvents used in the preparation of parenterals.

both use aqueous and non-aqueous solvents, vehicles, and co-solvents

Which of the following is an incorrect classification of parenteral preparations?

based on solid state

Which of the following is incorrect about small volume parenterals?

flexible but requires manipulation, large wastage

Which of the following excipients is NOT typically required for parenteral products?

bulking agent

Intraocular

located, occurring, or administered within the eyeball

Periocular

surrounding or located around the eye

Sub-tenon injection

a medical procedure where medication or anesthesia is delivered into the space between the sclera (the white of the eye) and the Tenon's capsule (the thin membrane covering the eyeball)

sub-conjunctival injection

a method of delivering medication directly into the space beneath the conjunctiva; the thin, clear membrane that covers the white part of the eye (the sclera) and the inside of the eyelids

inravitreal injection

a medical procedure where medication is shot directly into the eye

Large Volume Parenterals (LVPs) are typically used for:

Maintenance or replacement therapy via IV infusion

Small Volume Parenterals (SVPs) are defined as parenteral preparations with volumes:

100 mL or less

Which of the following ophthalmic dosage forms provides extended drug release and eliminates frequent dosing?

Drug-impregnated inserts

In ophthalmic formulations, increased viscosity leads to:

Increased retention and contact time in the eye

Ophthalmic dosage forms must be:

Sterile, isotonic, and free from pyrogens

Which of the following best defines parenteral preparations?

Sterile solutions or suspensions administered via injection

Which of the following is an example of a non-aqueous vehicle used in parenteral formulations?

Fixed vegetable oils

Which physiological factor primarily affects ophthalmic drug bioavailability?

Tear fluid turnover and contact time