Compounded Topical Pain Creams Review of Select Ingredients for Safety, Effectiveness, and Use (2020) / Chapter Skim
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Appendix C: Commissioned Paper: Topical Dosage Form Development and Evaluation
Appendix C: Commissioned Paper: Topical Dosage Form Development and Evaluation
Pages 257-278
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From page 257... ...
To understand the key mechanisms of topical drug delivery, the skin must be viewed as having two major layers: the outer epidermis and the inner d ermis. The epidermis lacks any blood vessels whereas the dermis has a rich network of blood vessels (see Figure C-1)
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From page 258... ...
Together, the tightly packed keratinocyte layers and intercellular lipids constitute the main barrier and keep external agents from penetrating into deeper layers of the skin. Melanin is the pigment responsible for skin color, and it protects the skin from intense ultraviolet (UV)
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From page 259... ...
The inter cellular lipids consist of ceramides, cholesterol, and fatty acids arranged in a bilayer lamellar pattern. SOURCE: Phospholipids aqueous solution structures by Mariana Ruiz Villarreal, LadyofHats is licensed under Creative Commons CC0.
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From page 260... ...
Some of the semisolid bases that are commonly used in compounding pain creams include premium lecithin organogel (PLO) , oleaginous base, Vanicream base, Aquaphor base, and Eucerin base.
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From page 261... ...
. Because a dense capillary network surrounds the sweat ducts and hair follicles, any small fraction of a drug that makes its way into the skin via the appendageal pathway will be quickly absorbed into the circulatory system, hence explaining why it is not available in effective amounts in the skin.
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From page 262... ...
PHYSICOCHEMICAL PROPERTIES OF ACTIVE PHARMACEUTICAL INGREDIENTS AND DERMAL ABSORPTION The most critical physicochemical characteristics that would influence the permeation of drugs across the skin are molecular weight, partition coefficient, melting point, and charge of the penetrant molecule. The molecules greater than 600 da are known to be poorly permeable across the skin (Barry, 2001)
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From page 263... ...
In a study reported by Ki and Choi, the authors observed greater permeation of the pain medication meloxicam ethanolamine compared to meloxicam, owing to the lesser melting point of the ethanolamine form (Ki and Choi, 2007)
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In topical products incorporated with poorly soluble drugs, an excess amount of drug is dispersed in the formulation due to saturation of the v ehicle. The suspended drug would act like a reservoir during absorption process.
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PHARMACEUTICAL EXCIPIENTS AND DERMAL DRUG DELIVERY The excipients play different functional roles, which in turn determine the type, structure, and stability of the semisolid base. Often, the excipients also affect the absorption of drugs.
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From page 266... ...
SKIN PERMEABILITY ENHANCERS The excipients used in the topical formulations are often intended to influence the skin permeability by interacting with the stratum corneum barrier. Some excipients are known to lead to hydration and swelling of the stratum corneum to enhance the drug delivery (examples include ropylene glycol, urea, and polyethylene glycol)
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From page 267... ...
For example, amitriptyline, one of the topical pain medications formulated in combination with other drugs, was found to permeate 4- and 5-fold more in the presence of fatty acids such as oleic acid and linoleic acid (Jain and Panchagnula, 2003)
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The buffer is filled in the flat bottom vessel and the paddle is used for stirring. SOURCES: PermeGear, 2018; © 2014 United States Pharmacopeial (USP)
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However, additional evidence is needed to demonstrate that porcine ear skin has comparable permeability characteristics to drug molecules as that of human skin. Excised human skin is most commonly obtained from cadavers or from patients undergoing plastic surgery.
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. TABLE C-1 Physicochemical Properties of APIs Commonly Used in Pain Medications Mol.
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From page 271... ...
. PERMEATION STUDIES OF PAIN MOLECULES Some studies in the literature have specifically discussed the permeation of APIs from topical pain products.
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From page 272... ...
Baclofen TABLE C-2 The Amount of Drug Absorbed Across the Human Cadaver Skin from Topical Pain Creams (n = 6 ± SD) % Absorbed (dose Active Pharmaceutical % w/w API in the Cream 50 mg of formulation Ingredient Formulation across 1.77 cm2 in 48 h)
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. It is evident from the above reports that APIs used in the compounded pain creams are poorly permeable and require appropriate enhancement strategies to improve their delivery into and across the skin.
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International Journal of Phar maceutics 41(1–2)
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2003. Transdermal drug delivery of tricyclic antidepressants: Effect of fatty acids.
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2000. Transdermal drug delivery: Overcoming the skin's barrier function.
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From page 277... ...
2013. Ex vivo percutaneous absorption of ketamine, bupivacaine, d iclofenac, gabapentin, orphenadrine, and pentoxifylline: Comparison of versatile cream vs.
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