An overview of veterinary compounding: Permeation-enhancing topical medications

A compounding pharmacist can provide insight on the uses and benefits of this revolutionary dosage form

Figure 1 (left): The patented ‘Topi-Click Micro’ device with rounded applicator. Figure 2 (right): Topical delivery of a permeation-enhancing gel using an applicator device. Images courtesy PCCA Science
Figure 1 (left): The patented ‘Topi-Click Micro’ device with rounded applicator. Figure 2 (right): Topical delivery of a permeation-enhancing gel using an applicator device.
Images courtesy PCCA Science

Veterinary compounding, the preparation of customized medications to meet the individual needs of animals, plays a key role in current therapeutics. Specifically, permeation-enhancing compounded gels represent a promising dosage form—one which is non-invasive, easy to administer, and, as such, likely to increase treatment compliance.

These topical medications are expected to allow for the percutaneous absorption of drugs into and through the animal’s skin, bypassing the first-pass metabolism and allowing for greater bioavailability, as well as decreased dosing, to achieve therapeutic effects.

One or more active pharmaceutical ingredients may be incorporated into a permeation-enhancing base (e.g. pluronic lecithin organogel [PLO], Lipoderm) for topical application using a medical device. While indicated in multiple therapeutic categories, permeation-enhancing topical medications are widely used in pain management.

Practical application

Figure 3: Rate of percutaneous absorption (mean flux) for tramadol permeation-enhancing gels when applied in vitro to the inner ear of domestic feline skin (adapted from Bassani et al, 2015b).
Figure 3: Rate of percutaneous absorption (mean flux) for tramadol permeation-enhancing gels when applied in vitro to the inner ear of domestic feline skin (adapted from Bassani et al, 2015b).

The veterinary population is wide, diverse, and complex. The right medicine for the right animal is not always available due to the lack of commercial medicines and issues with compliance. As such, veterinarians, caregivers, and pet owners often struggle to administer medicines to animals of all sizes, and across all species.

Veterinary compounding plays a key role in meeting the individual needs of animals by providing customized medications addressing the unique issues and challenges of the veterinary population. Compounding pharmacists in Canada are well capable to prepare these customized medicines, from chicken-flavoured oral suspensions to chewable animal treats and permeation-enhancing (transdermal) gels.

Pain management is a particularly challenging therapeutic category in veterinary medicine. This is largely due to the different origins and types of pain, which makes the condition difficult to diagnose and treat. The transdermal delivery of active pharmaceutical ingredients (APIs) is a promising route of administration when managing both acute and chronic pain.

Compared to intravenous and subcutaneous administration, transdermal delivery is a non-invasive route allowing for the percutaneous absorption of drugs into and through the animal’s skin. Following application, the drugs are intended to be directly absorbed into the systemic circulation over a period of time, bypassing the first-pass metabolism and allowing for greater bioavailability and decreased dosing to achieve therapeutic effects.

Likewise, compared to oral administration, permeation-enhancing topical medications are easy to administer and, thus, more likely to increase compliance.1,2 These medications are intended for external use only and application is recommended by means of a metered topical applicator (Figure 1). This medical device is used to accurately and easily micro-dose topical medications for humans and animals.

Prepared by compounding pharmacists according to a doctor’s prescription, topical compounded medications are created by adding APIs (alone or in combination) to permeation-enhancing bases, such as PLO or Lipoderm.

PLO is a first-generation base composed of two phases, the pluronic phase (aqueous) and the lecithin phase (oily), which are continuously mixed until a homogenous gel forms. This gel is intended to dissolve both hydrophobic and hydrophilic drugs, with hydrophobic drugs dissolving in the oil phase and hydrophilic drugs dissolving in the aqueous phase.3

Meanwhile, Lipoderm was the first proprietary permeation-enhancing base in the compounding industry, as well as the most-studied one. It consists of a proprietary liposomal component shown to successfully facilitate the penetration of drugs into and through ex vivo human skin under in vitro conditions.4-8 A particularly interesting in vitro study predicted the in vivo rate and extent of absorption of tramadol, a synthetic opioid, when managing pain in domestic felines. According to Bassani et al., PLO and Lipoderm facilitated the percutaneous absorption of tramadol 100 mg/g across the skin of domestic feline inner ear, with a peak rate of absorption at approximately two and half hours, followed by a steady decline in rate over time (Figure 3).6 Simmons et al. conducted a systematic literature review to evaluate the use of Lipoderm in compounded medications for veterinary patients and found scientific evidence to support the topical application of these permeation-enhancing gels.9

Conclusion

Permeation-enhancing topical medications are a landmark in veterinary pharmacotherapy. Table 1 displays a selection of commonly prescribed, permeation-enhancing compounded options for veterinary patients from different therapeutic categories. A formula example for diltiazem five per cent used in veterinary patients is shown in the International Journal of Pharmaceutical Compounding.10 A compounding pharmacist can provide further information and insight on the uses and benefits of this revolutionary dosage form.

Commonly prescribed permeation-enhancing compounded options for veterinary patients from different therapeutic categories.
Commonly prescribed permeation-enhancing compounded options for veterinary patients from different therapeutic categories.

APPLYING PERMEATION-ENHANCING GELS

  1. Put on gloves or a finger cot prior to application of the gel.
  2. Turn the bottom of the Topi-Click Micro device to the prescribed amount of clicks to obtain the dose. Each click of the device delivers the volume of 0.1 ml.
  3. The dose may be applied using one of two methods: apply to gloved finger and then massage into the area of the ear where there is the least amount of fur (Figure 2) or, if the device has an angled or pointed tip, apply the gel directly to the ear. Other areas of the pet’s body may be used (e.g. the scruff or underneath the armpits), according to the veterinarian prescription.
  4. Massage the gel in thoroughly for at least 20 to 30 seconds. When finished, check the area to make sure no gel is left to rub in.
  5. If wearing gloves, wash hands with gloves on, dry, then remove. Wash hands again. If using a finger cot, remove inside out and dispose of properly, then wash hands.
  6. Prior to the next application, after donning gloves or a finger cot, remove any residue from the previous application with a wet paper towel and a small amount of soap or alcohol.

Maria Carvalho, PharmD, MRPharmS, PhD, is a U.K.-qualified Portuguese pharmacist with a PhD in personalized medicines from the University College of London. In her 15 years of experience, Dr. Carvalho has practiced in community pharmacy, hospital pharmacy, and the pharmaceutical industry in Europe and the United States. She is the manager of PCCA Science at the Professional Compounding Centers of America (PCCA).

Sebastian Denison, BSc., PharmD, is a clinical compounding pharmacist with PCCA. A lifelong dog-owner and animal-lover, Denison previously worked in North Vancouver, B.C., in a compounding pharmacy, specializing in hormone replacement therapy, pain management, veterinary medicine, and sports medicine.

A.J. Day, PharmD, is vice-president of clinical services at PCCA in Houston, Texas. His practice focus areas include regulatory affairs, compounding supply chain, veterinary compounding, pediatric medicine, aseptic compounding, and pain management.

References

1 Branvold, A. and Carvalho, M. (2014) ‘Pain Management Therapy: The Benefits of Compounded Transdermal Pain Medication,’ Journal of General Practice, 2 (6), doi: 10.4172/2329-9126.1000189.

2 Bucher, C.V., Day, A.J. and Carvalho, M. (2018) ‘The Role of Transdermal Compounding in Opioid Safety,’ Journal of Opioid Management, 14 (1), p.17-22.

3 Belgamwar V, Chauk D, Pandey M and Surana S. (2008) ‘Pluronic lecithin organogel.’ Asian Journal of Pharmaceutics, 2, 134.

4 Bassani, A.S., Banov, D. and Lehman, P.A. (2008) ‘Evaluation of the Percutaneous Absorption of Promethazine Hydrochloride, In Vitro, Using the Human Ex Vivo Skin Model,’ International Journal of Pharmaceutical Compounding, 12 (3), p. 270-273.

5 Bassani, A.S., Banov, D. and Phan, H. (2015a) ‘In Vitro Characterization of the Percutaneous Absorption of Lorazepam into Human Cadaver Torso Skin, Using the Franz Skin Finite Dose Models’, Journal of Pharmaceutics and Drug Delivery Research, 4(2), p. 1-5, doi: 10.4172/2325-9604.1000131.

6 Bassani, A.S., Banov, D., Simmons, C. and Phan, H (2015b) ‘In vitro characterization of the percutaneous absorption of tramadol into inner ear domestic feline skin using the Franz skin finite dose model,’ Veterinary Medicine and Animal Sciences, 3 (3), doi: 10.7243/2054-3425-3-3.

7 Bassani, A.S. and Banov, D. (2015c) ‘Evaluation of the Percutaneous Absorption of Ketamine HCl, Gabapentin, Clonidine HCl, and Baclofen, in Compounded Transdermal Pain Formulations, Using the Franz Finite Dose Model,’ Pain Medicine, 17 (2), p. 230-238, doi: 10.1111/pme.12899.

8 Bassani, A.S., Banov, D. and Phan, H. (2016) ‘Characterization of the Percutaneous Absorption of Ketoprofen Using the Franz Skin Finite Dose Model’, Postgraduate Medicine, 128 (2), p. 262-267, doi:10.1080/00325481.2016.1144448.

9 Simmons, C., Edwards, C., Carvalho, M. and Day, A.J. (2018) ‘The use of Lipoderm as a transdermal base in veterinary compounding: A systematic literature review’, British Small Animal Veterinary Association (BSAVA) Congress 2018, Poster Presentation. Birmingham, UK 5-8 April.

10 Allen, L.V. (2008) ‘Diltiazem 5% in Lipoderm, Veterinary’, International Journal of Pharmaceutical Compounding, 12 (1), p. 67.

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