Excipients for solubility/dissolution and permeation enhancement

1. Excipients for
solubility/
dissolution and
permeation
enhancement
Solubility Enhancer
Permeation Enhancer

2. Solubility Enhancer

3. Need/Purpose
• Some of the API shows poor solubility in solvents
• Some of the API shows poor permeability across biological membrane
• Both of above problems results in poor bioavailability
• Hence there is a need to enhance solubility and permeability of API to
improve bioavailability

4. Principle for solubility/ dissolution enhancement
• Solubility/dissolution of an API could be enhance through processes
of solubilization
• Solubilization is the processes of passage of poorly water soluble
solute into an aqueous solution of surfactant to form
thermodynamically stable solution.
• E.g. Surface active agents/surfactants: Poly(ethylene glycol) (PEG),
Propylene Glycol

5. Solubility Enhancer
(PEG 200)
• Polyethylene glycol (PEG) is a polymer composed of repeating units of
the monomer ethylene oxide. Liquid grades (PEG 200–600) occur as
clear, colorless or slightly yellow-colored, viscous liquids.
• Lower-molecular-weight grades (PEG 200, PEG 400) are preferred as co-
solvents in pharmaceutical solutions.
• Polyethylene glycols can also be used to enhance the aqueous solubility
or dissolution characteristics of poorly soluble compounds by making
solid dispersions with an appropriate polyethylene glycol.
• Stability: Polyethylene glycols are chemically stable in air and in solution
• Safety: Generally, they are regarded as nontoxic and nonirritant
materials. The most serious adverse effects are hyperosmolarity,
metabolic acidosis, and renal failure following the topical use of
polyethylene glycols in burn patients

6. Permeation
Enhancers

7. Permeation Enhancers
• Permeation enhancers are those substances which promote the
absorption of drug through the skin temporarily by transiently
enhancing the skin permeability.
• Mechanism: Penetration enhancers causes disruptions in the highly
organized structure of stratum corneum
• They are employed to transfer the delivery of drugs which are
ionizable (Example: timolol maleate) and impermeable (Example:
heparin); to maintain drug levels in blood through transdermal drug
delivery system
• ijpsr.com/bft-article/review-article-on-permeation-enhancers-a-
major-breakthrough-in-drug-delivery-technology/?view=fulltext

8. Ideal properties of Permeation Enhancers:
• These materials should be biocompatible i.e. it should not cause irritation or
any allergic response both in the short as well as the long run.
• Also it should not induce toxicity
• It should be compatible with the drug and possess good solvent properties.
• It should not exhibit any adverse pharmacological activity inside the body.
• It should not be expensive.
• It should not have color, odor and taste.
• It should be stable chemically as well as physically.
• It should not cause leakage of body fluids and endogenous materials
(unidirectional flow), and as soon as such substances are removed, the skin
should immediately restore its natural barrier properties.

9. Examples of Permeation Enhancers
• Propylene glycol
• Cyclodextrines
• Dimethyl sulfoxide
• Surface active agents: Cationic surfactants, Anionic surfactants
• Terpenes: Terpenes and terpenoids