How to improve topical formulations of poorly-water soluble APIs

Solubility of an Active Pharmaceutical Ingredient (API) in the dosage form is a key parameter in topical formulation. Poor solubility can negatively impact the API drug load, its stability in the dosage form as well as its skin permeation behavior.

Polar solvents such as PEG-400, diethylene glycol monoethyl ether or propylene glycol are commonly-used to successfully raise the  solubility of the API in the dosage form. However they are also notoriously difficult to stabilize and have a negative impact on the drug texture.

Highlights

Use of polar solvents is an efficient way to improve solubility of topical APIs

Inverse latex and associative polymers can stabilize high concentration of polar solvents

Within flexible formulation settings of pH and temperature

In conventional as well as innovative dosage forms with formulation and patient benefits

Inverse latex and associative polymers have demonstrated high thickening and stabilization capacity of polar solvents, with successful application in commercialized drugs. In these experiments stable formulas with high solvent concentration were achieved, using solvents of different natures (50% PEG 400, 40% of diethylene glycol monoethyl ether, 60% of a solvent mix…).

Their polymeric network not being impacted by pH (even acid pH) nor temperature further helps formulation scientists to maximize the solubility of their APIs by process adjustment.

Innovative dosage forms with formulation and texture benefits were developed using inverse latex and associative polymers. Cream-gels, biphasic systems stabilized these polymers without surfactant addition, was used to simultaneously stabilize 25% of solvent and 30% of oil phase. Gel-in-oil emulsion exhibited very interesting properties of solvent stabilization with a unique sensorial profile.

Read the Seppic articles

Looking for effective solubilizers? Find out about Seppic’s Polysorbate range here or continue reading and order a sample directly from below table.

The MONTANOX™ range is composed of different grades of polysorbates that can be used to solubilize active pharmaceutical and/or biological ingredients and to formulate oil-in-water emulsions for oral, topical and injectable products.
The triple action of polysorbates MONTANOX™ products are polyethoxylated sorbitan esters.
These hydrophilic surfactants play a triple role: They are used as emulsifiers to formulate oil in water emulsions but also as solubilizers for active ingredients with low solubility and also as antiaggregants for biological active ingredients. MONTANOX™ products are stable in acidic or basic media and in the presence of electrolytes and are compatible with other surfactants.
They can be combined with MONTANE™ to produce highly stable emulsions.

A suitable grade for every application
The MONTANOX™ range is composed of monoesters of lauric, stearate or oleic fatty acids. They each have a degree of ethoxylation of 20 and are characterized by their HLB (Hydrophilic-Lipophilic Balance).
There are two pharmaceutical grades: PPI and PHA PREMIUM.
The PPI grade is designed for injectable administration and products are manufactured according to the Good Manufacturing Practices “GMP part II” and comply with the EP, USP and JP or JPE pharmacopoeia.
The PHA PREMIUM grade is designed for oral and topical administration and products are manufactured according to IPEC’s GMPs and comply with the EP and USP pharmacopoeia.

*API: very low water quantity
** LPI: grade with low pH