The Formulation and Evaluation of Topical Berberine-Hydrochloride Products

The authors sought to prepare a topical formulation of berberine hydrochloride for the effective and controlled management of inflammation and skin infections.
Jan 02, 2010
Volume 34, Issue 1

Berberine hydrochloride (BRB) is an isoquinoline-alkaloid derivative that can be isolated from medicinal herbs such as Hydrastis canadensis (goldenseal), Cortex phellodendri (huangbai), and Rhizoma coptidis (huanglian) (1). In the Chinese Pharmacopoeia, huangbai and huanglian are described as heat-removing agents for fever reduction (2). BRB, the major ingredient of these herbs, possesses antimicrobial activity against Gram-positive and Gram-negative bacteria, as well as against other microorganisms (3, 4). BRB inhibits the growth of streptococci and appears to prevent them from adhering to host cells (5). BRB also exhibits antimalarial, antisecretory, anti-inflammatory, and anticancer activities with relatively low cytotoxicity to human cells (6).

Topical and transdermal products are important classes of drug-delivery systems, and their use is becoming more widespread. The purpose of topical dosage forms is to deliver drugs conveniently to a localized area of the skin (7). Topical creams (e.g., cold cream), which are oil-in-water (O/W) emulsions, are less greasy and more acceptable to patients. Patients generally prefer creams for the treatment of mild or short-duration conditions (8).

Many topical antifungals are now available, but not all are equally effective. Only a few topical antibiotics are available for treating skin diseases (9, 10). The authors investigated cream formulations of BRB because it possesses antifungal, antibacterial, and anti-inflammatory activity.

Apifil (PEG-8 Beeswax, Gattefossé, St. Priest, France) and Plurol Stearique WL 1009 (polyglyceryl-6-distearate, Gattefossé) were selected as O/W emulsifiers. Both emulsifiers can be used to formulate creams with various concentrations of the oil phase without phase inversion. At higher concentrations (e.g., 5–15%), they form stable creams with a firm texture and a smooth, glossy appearance. The agents emulsify vegetable oils by as much as 15% are particularly well-suited to the emulsification of short-chain or fatty-acid esters. They perform well with other fatty-acid esters, silicone oils, mineral oils, and their substitutes.

The authors attempted to develop safe topical formulations of BRB that could deliver the drug locally in an effective concentration for its antimicrobial and anti-inflammatory effects. The effectiveness of the cream formulation would likely depend on the nature and concentration of the emulsifier used, on the concentration of BRB, and on the storage time of the cream formulations. The authors designed an experiment to investigate the effects of these variables on the formulation of BRB as a topical drug-delivery system.

Materials and methods

Plant materials. BRB HCl powder (90% purity) was received as a gift from Yucca Laboratories (Mumbai) and used in the study without further purification procedures.

Formulation materials. The authors chose the emulsifiers Apifil and Plurol Stearique WL 1009 for formulating the BRB creams. Both emulsifiers were obtained from Gattefossé. The formulations were based on aqueous cream BP (British Pharmacopoeia). The formulation for 100 g of aqueous cream BP was the following:

  • Emulsifying Ointment BP (30 g)
  • Phenoxyethanol BP (1 g)
  • Boiled and cooled purified water (100 g).

Table Ia: Composition of topical cream formulations of BRB prepared without permeation enhancer (%w/w).
Emulsifying ointment BP consists of emulsifying wax BP (30%), white soft paraffin BP (50%), and liquid paraffin BP (20%), and acts as a hydrophobic vehicle, structural-matrix former, and emulsifying agent. Menthol BP was used as a permeation enhancer. The detailed composition of different cream formulations is shown in Tables Ia and Ib.

Microorganisms. Two microorganisms, Staphylococcus aureus (MTCC 96) and Candida albicans (MTCC 227), were chosen to test the effectiveness of the BRB cream formulations.

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