Adapalene pretreatment increases follicular penetration of clindamycin

Gaurav K Jain, Farhan J Ahmed

Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi - 110 062, India

In the clinical management of acne vulgaris, a considerable number of topical and/or systemic treatment modalities are available to the physician. The combination of a topical antibiotic with a topical retinoid is a rational choice because of their distinct, complementary and additive mechanism of action. Topical retinoids have a dual mechanism of action. They possess a strong anticomedogenic effect and are effective against inflammatory acne lesions. ^[1] Topically applied retinoids are an integral component of combination therapy for acne vulgaris because they promote comedonal drainage, which facilitates the penetration of other topical agents through the follicular pathway. ^[2],[3] 

Clinical experience has shown that adapalene, a new topical retinoid, has a superior cutaneous safety profile and could be used in combination with other topical agents without any significant additive irritant effect. ^[4] Mechanistically, adapalene binds to specific retinoic acid nuclear receptors and normalizes the differentiation of follicular epithelial cells resulting in decreased microcomedone formation. ^[5],[6] Topical antibiotics such as clindamycin reduces Propionibacterium acnes count and inhibits the inflammation caused by the bacteria. ^[7] However, clindamycin phosphate is less effective because of its low solubility and consequent difficulty in penetrating the sebum-filled follicles. ^[8] Some percutaneous absorption may also occur with clindamycin phosphate, resulting in diarrhea and colitis. ^[9] In the present study, the effect of adapalene (when applied concomitantly or after a time duration) on the follicular penetration of clindamycin phosphate is evaluated.

In vivo scintigraphic studies in human volunteers 

A total of 30 healthy male volunteers (age: 25 ± 5 years), were enrolled in the study. Subjects with abnormal skin hyperpigmentation, a history of skin disease or known sensitivity to skin care products were excluded from the study. Use of any systemic drug and/or topical drug on the application area within one week before beginning the protocol was not permitted. Radiolabeled clindamycin phosphate gel at a target dose of 5mg/dose/cm ² was applied concomitantly to the hand of healthy human volunteers and after pre-treatment of the skin for 3, 5 and 10 min with 10 mg of adapalene gel per cm ² . After completion of the study, subjects were monitored up to one week for skin irritation, adverse effects or any systemic effects. 

Result

As shown in [Table - 2], adapalene increases the penetration of clindamycin phosphate. Significantly higher concentrations of clindamycin phosphate (19%) in skin were achieved following the pretreatment of skin with adapalene for 5 min as compared to the control (7.2%, P<0.05). None of the volunteers in either treatment group experienced any local and systemic adverse reactions (pseudomembranous colitis and diarrhea).

DISCUSSION

The concomitant application or the pretreatment of skin with adapalene gel promotes comedonal drainage that allows the follicle to function as rapid transport shunts and permit high concentrations of clindamycin phosphate to bypass the continuous stratum corneum and readily reach the deeper viable skin layers. The microcrystals of adapalene rapidly distributes in the upper part of follicular duct within 3-5 min of topical application of the adapalene 0.1% gel; therefore, the pretreatment of skin with adapalene gel for 5 min prior to application of clindamycin gel significantly increases the penetration of clindamycin phosphate.

As shown in this study, the characteristic property of adapalene to enhance the penetration of clindamycin phosphate into skin makes it a good choice as a therapy in combination with clindamycin phosphate for the treatment of acne. Adapalene increases the follicular penetration of clindamycin phosphate, thereby enhancing its localization in the skin. The application of clindamycin phosphate gel after the pretreatment of skin with adapalene gel may contribute significantly to the increased efficacy of therapy.

(Source: https://www.ncbi.nlm.nih.gov/pubmed/17921613)

References