Pharmacy Courses

Surfactant Selection for Dissolution Study of Poorly Soluble Drug

Surfactants are substances which tends to reduce the surface tension between two liquids, between a gas and a liquid, or between a liquid and a solid in which it is dissolved easily. Surfactants may act as detergents, wetting agents, emulsifiers, foaming agents, or dispersants.

Surfactants play an active rule in pharma industry, especially for poorly soluble drugs. The properties of surfactants are such that they can alter the thermodynamic activity, diffusion, disintegration, solubility and dissolution rate of a drug, which influences the rate and extent of drug absorption. So it's important to know how to choose a surfactant for dissolution study of poorly soluble drug.

  • Non-ionic surfactants (which do not undergo ionization when being dissolved in water): Polyethylene glycol (PEGs)
  • Anionic surfactants: sodium lauryl sulfate, ammonium lauryl sulfate
  • Cationic surfactants: quaternary ammonia compounds with positively charged surface-active moieties (benzalkonium, benzethonium, cetylpyridinium, methylbenzethonium)

As per USP General Chapter 1092

Physical and chemical characteristics of the drug substance need to be determined as part of the process of selecting the proper dissolution medium. When deciding the composition of the medium for dissolution testing, it is important to evaluate the in§uence of buffers, pH, and if needed, different surfactants on the solubility and stability of the drug substance. 

Typical media for dissolution may include the following (not listed in order of preference): 

  • diluted hydrochloric acid, buffers (phosphate or acetate) in the pH range of 1.2–7.2
  • simulated gastric or intestinal §uid (with or without enzymes) and
  • water
Aqueous solutions (acidic or buffer solutions) may contain a surfactant to enhance the solubility of the drug substance. The surfactants selected for the solubility investigations should cover all common surfactant types, i.e., anionic, nonionic, and cationic. When a suitable surfactant has been identi¦ed, different concentrations of that surfactant should be investigated to identify the lowest concentration needed to achieve sink conditions. Typically, the surfactant concentration is above its critical micellar concentration (CMC). 

A list of some of the surfactants used in dissolution media with CMC value (%):
  • Sodium lauryl sulfate (SLS) (0.18–0.23)%
  • Taurocholic acid sodium salt 0.2%
  • Cholic acid sodium salt 0.16%
  • Desoxycholic acid sodium salt 0.12%
  • Cetyltrimethyl ammoniumbromide (CTAB, Hexadecyltrimethylammonium bromide) (0.033–0.036)%
CMC values are dependent on medium and temperature. The list is not comprehensive and is not intended to exclude surfactants that are not listed. Other substances, such as hydroxypropyl β-cyclodextrin, have been used as dissolution media additives to enhance dissolution of compounds with low solubility. It is important to control the grade and purity of surfactants because use of different grades could affect the solubility of the drug. For example, sodium dodecyl sulfate (SDS) is available in both a technical grade and a high-purity grade. Obtaining polysorbate 80 from different sources can affect its suitability when performing HPLC analysis. The USFDA and USP maintain databases of dissolution methods, including information on dissolution media that have been used. 

The role of surfactants is very diverse and critical in the development of pharmaceutical formulations. Depending on their charge characteristics the surface-active molecules may be anionic, cationic, zwitterionic (ampholytic) or non-ionic.
  • Sorbitan esters are supplied commercially as Spans and are mixtures of the partial esters of sorbitol and its mono- and di-anhydrides with oleic acid. They are generally insoluble in water (low hydrophile–lipophile balance (HLB) value) and are used as water-in-oil emulsifi ers and as wetting agents. 
  • Polysorbates are complex mixtures of partial esters of sorbitol and its monoand di-anhydrides condensed with an approximate number of moles of ethylene oxide. They are supplied commercially as Tweens. The polysorbates are miscible with water, as refl ected in their higher HLB values, and are used as emulsifying agents for oil-in-water emulsions. 
  • Poloxamers are synthetic block copolymers of hydrophilic poly(oxyethylene) and hydrophobic poly(oxypropylene).

The safety aspects of newly developed surfactants must be ensured before their incorporation in therapeutic dosage forms. A wide variety of drugs, including the antihistamines and the tricyclic depressants, are surface-active.

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