Transdermal gel delivery in cats: fuss or must? (Proceedings)


Transdermal gel delivery in cats: fuss or must? (Proceedings)

Compounded transdermal pluronic-lethicin organo (PLO) gels have become a popular method of drug delivery widely embraced by the veterinary profession, despite the lack of scientific evidence in support of this system. The PLO gels were developed as a practical alternative to traditional drug delivery systems. Descriptions of the gels cannot be found in the scientific literature but are limited to class materials and other non-referenced literature distributed to educators such as Professional Compounding Companies of America.e

The gels are comprised of water-based compounds prepared in various organic solvents. The oil phase is composed of lecithin (generally of soy bean origin) which theoretically re-arranges the stratum corneum, the major barrier to drug movement across the skin. Isopropyl palmitate acts as a solvent and penetration enhancer. The water phase is comprised of purified water and a pluronic (poloxamer) gel comprised of a surfactant (pluronic F127), which also contributes to disruption of the stratum corneum. Because lecithin promotes the growth of mold, potassium sorbate is included as a preservative.36 The active drug ingredient is dissolved in either the oil (lipid) or water phase, depending on its lipid solubility. The amount of active drug added is based on the recommended dose; generally, the gel is designed such that the dose is delivered in 0.1 ml (cats and small dogs) to 0.5 to 1 ml (larger dogs). Lecithin and isopropyl palmitate (a ratio of 1:1) must comprise at least 24% of the system in order for micelles containing the drug to form properly. The remaining volume of a PLO gel is comprised of the drug and the pluronic gel. Because manufactured drug preparations often are not available in concentrations sufficient to allow delivery of the calculated dose in the small volume of PLO, purified bulk powder (which is not legal) is preferred by compounding pharmacies formulating the gels. When subjected to proper shearing forces (generally accomplished by rapidly passing the mixture between a small caliber catheter or two syringes; Figure 3), micelles containing the drug theoretically are formed. The micelles are believed to slightly disorganize the stratum corneum with minimal direct detrimental effects on the skin (based on light microscopy), although contact hypersensitivity or allergy to the lecithin component may occur (see below).37, 38 The PLO gel is appears to dissolve a variety of different chemicals, including lipophilic, hydrophilic and amphoteric compounds. The gels can be easily and rapidly prepared and theotretically are stable in most clinic environments. However, the gels are thermoreversible: at temperatures above 40┬░C, they are liquid, but they become high-viscosity gels following cooling to room temperature and remixing. At refrigerated temperatures, the gels again become liquid. Thus, the PLO gel becomes more viscous at higher temperatures, rendering it more amenable to topical drug delivery.

At least two PLO gels (ie, with the pluronic and oil phases already mixed) are commercially available: Lipoderm® is sold by Professional Compounding Pharmacies of America (PCCA). This organization offers compounding training classes for pharmacists, including formulation of PLO gels and recipes for the preparation of many different drug products as gels. The advent of PLO gels as a method of systemic drug delivery and the formulation of the original PLO gel was generated through the PCCA division of research.e In addition to training, PCCA sells validated ingredients to be used in compounding. However, sale and compounding guidance is limited to PCCA members; membership at the time of publication of this article costs $20,000. The financial incentive for PCCA to train pharmacists in the compounding of PLO gels intended for veterinary use is obvious. Products for formulation of PLO gels are also available through other companies (eg, Gallipot which sells a commercial PLO base as well as drugs, and chemical companies which sell pure drugs). The products that PCCA offers for sale has drawn the attention of the Food and Drug Administration: a warning letter was sent in 2001 regarding their sale of bulk substances, including dipyrone and antibiotics.d

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