A New Paradigm for Improving Oral Absorption of Drugs in Discovery: Role of Physicochemical Properties, Different Excipients and the Pharmaceutical Scientist

Figures & data

Figure 1. Biopharmaceutics Classification System.

Figure 2. Changing paradigm in early formulation development.

PD: Pharmacodynamic; PK: Pharmacokinetic.

Table 1. Excipients employed in oral liquid formulations.

Class of excipients	Examples	Advantages and limitations
In situ salt formation	Strong acids and bases, such as hydrochloric acid, sodium hydroxide	Viable strategy in drug discovery that potentially improves solubility by forming salts.
pH adjustment	Buffers, such as citrate, phosphate, carbonate	Buffers are useful in controlling the pH of the formulation to improve and maintain solubility. Buffers with lower buffer capacity are often well tolerated, but those with high buffer capacity may cause irritation.
Surfactants	Tween 80, Solutol HS, Labrasol, Cremophor, Vitamin E TPGS, Pluronic F68	Surfactants are useful in enabling solubility, improving wetting and dissolution, reducing compound precipitation. They may cause histamine release in some animal species.
Co-solvents	Polyethylene glycol 400 (PEG 400), polyethylene glycol 300 (PEG 300), propylene glycol, ethanol, glycerin	Co-solvents are very useful in solubilizing lipophilic compounds. Many co-solvents, such as PEGs and PG are osmotic agents and can cause GI disturbances when used in high concentrations and/or for a longer period of time.
Cyclodextrins	Captisol^®, Hydroxypropyl β cyclodextrin	Cyclodextrins are very useful in solubilizing lipophilic compounds by complexation. Many cyclodextrins have a potential for causing nephrotoxicity and GI disturbance when used in high concentrations and/or for a longer period of time.
Lipids	Corn oil, Olive oil, Miglyol 812	Lipids are very useful in solubilizing lipophilic compounds. They may be used alone or in combination with surfactants to form self-emulsifying drug delivery system formulations, potentially improving exposure. Multiple administrations of lipid formulations could result in altered lipid profiles and could cause GI disturbances.
Suspending agents	Methylcellulose, sodium carboxymethyl cellulose	Suspending agents are either used alone or in combination with surfactants. They are useful in limiting dose variability of poorly soluble compounds.

GI: Gastrointestinal; PEG: Polyethylene glycol.