1172vol11.1 acne

VOLUME 11
Secundum
Artem Current & Practical Compounding
BASICS OF COMPOUNDING
GOALS AND OBJECTIVES
Goal: To provide pharmacists, pharmacy students and pharmacy technicians supportive information on the basics of
compounding solutions for the prevention and treatment of acne.
Objectives: After reading and studying the article, the reader will be able to:
1. Explain the causative factors related to acne.
2. Discuss the basic treatment regimens for acne.
3. Describe the various lifestyle factors that can cause acne.
4. List various compounded formulations that are being used in the treatment of acne.
These units are made up of a hair follicle, sebaceous glands NTRODUCTION
and a duct (pilosebaceous duct) connecting it to the skin sur- Acne is an inflammatory follicular, papular, and pustular face through which the hair shaft passes. Epithelial tissue eruption involving the pilosebaceous apparatus.1 There are forms the lining of this shaft. During normal operation, the many types of acne with acne vulgaris the most common.
sebaceous glands produce sebum that passes to the skin sur- Acne vulgaris is an eruption, predominantly of the face, face through the ducts spreading over the skin to minimize upper back and chest, composed of comedones, cysts, water loss and to maintain skin and hair hydration. Sebaceous papules and pustules on an inflammatory base. Acne occurs glands are more common on the face, back and chest, where in almost all individuals at some time or another and is one of the most widespread medical conditions in the world, yet During prepuberty, there is relatively little activity from the there is no cure. It has been said that there is no single condi- sebaceous glands. However, as both males and females tion that causes more psychic trauma, maladjustment, approach puberty, androgenic hormones increase and, as a general insecurity, feelings of inferiority and other psychic result, sebaceous glands are stimulated. During puberty, an increase in androgens is closely related to The incidence is approximately 85% between the ages of 12 four processes involved in acne development, including (1) an and 24 years. It typically occurs in males aged 16 to 18 and in abnormal keratinization of cells in the pilosebaceous duct, (2) females about a year earlier. In the mid-teen years, papular and increase in sebum production, (3) an accelerated growth lesions generally occur and nodular lesions in the late teens.
of Propionibacterium acnes, and (4) the occurrence of inflamma- By the mid 20s, it generally clears in males but may persist into the 30s in women and worsen during menopause.3,4 In With an increase in keratinization of cells shed in the duct and the US, it is estimated that 60% of the teenagers use OTC an increase in their cohesiveness, an obstruction of the follicle occurs, rather than the normal migration and removal of thecells from the skin surface. The entrapped and keratinized cells cause the follicle to expand and form a microcomedo, CNE FORMATION
which is the beginning of the acne lesion. As the process con- Acne is related to hormones, sebum, follicle fallout, bacteria tinues and additional cells and sebum accumulate, the and inflammation and begins in the pilosebaceous units(hair follicle and associated sebaceous glands) in the dermis.
Quest Educational Services Inc. is accredited by the Accreditation Council for Pharmacy Education as a Loyd V. Allen, Jr., Ph.D., R.Ph., Professor Emeritus, provider of continuing pharmaceutical education.
University of Oklahoma, HSC College of Pharmacy, This lesson is no longer valid for CE credit after 08/01/05.
microcomedo enlarges and becomes visible as a closed come- ty. Environmental factors, such as high humidity and heat do, or whitehead and becomes visible as a small, pale nodule and other conditions that cause frequent and prolonged just beneath the skin surface. This lesion is the precursor to fur- sweating can exacerbate acne. Tight fitting clothes that restrict air movement and prevent evaporation of skin moisture also As the lesion progresses and additional material accumulates, increase skin hydration and contribute to acne. Also, acne can the plug is pushed towards the surface resulting in an open be aggravated by headbands, helmets and friction-producing comedo, or blackhead. The color of the blackhead may be due devices or positions such as resting the chin or cheek on the to the presence of melanin in the plug. In the duct, P. acnes, an hand often and for long periods of time. Also, exposure to anaerobic rod and the primary microorganism found in the dirt, cooking oils/vapor/smoke or industrial chemicals such duct, undergoes accelerated growth. Through lipase produc- as petroleum derivatives can cause occupational acne.
tion and the breakdown of the sebum to free fatty acids, an Acne resulting from cosmetics is usually of the closed, nonin- inflammatory reaction occurs, contributing to inflammatory flammatory type and is more common in women. Products acne lesions and localized tissue destruction.
that contain oils (lanolin, mineral oil, cocoa butter) are come- As the plug grows and the inflammatory processes continue, dogenic, being occlusive and plugging the folicles inflammation of the duct wall develops resulting in a disrup- exacerbating or even initiating acne. Hair spray can occlude tion of the epithelial lining and lymphocyte infiltration. If the the pilosebaceous gland and cause acne.
follicle ruptures, spontaneously or by squeezing or picking, a Emotional factors contributing to acne may include severe or severe inflammatory reaction can occur. During squeezing or prolonged periods of stress or other emotional extremes, but picking, the contents of the plug can be discharged into the surrounding tissue resulting in abscesses that may result in Hormonal factors are evidenced by premenstrual flare-ups.
scars or pits after healing. Inflammatory acne, with pustules or Androgenic progestins, as in some oral contraceptives, are purulent nodules, are more likely to cause scarring than non- contributors to acne, as are some cyclic progestins used in menopausal hormone replacement therapy.
Acne is characterized by whiteheads, blackheads, acne pim- Some medications can exacerbate pre-existing acne but will ples and acne blemishes. Closed or open comedones, not actually cause a true acne. Drugs that may contribute to or (whiteheads and blackheads) are characteristic of noninflam- induce acne eruptions include corticosteroids (systemic and matory acne. Typically, a patient with acne will experience a topical), androgens, azathioprine, bromides, contraceptives combination of open and closed comedones, papules and pus- with a high progestin level, corticosteroids, dantrolene, disul- tules, typically on the face, chest and back but are not limited firam, ethionamide, haloperidol, halothane, iodides, to these areas. Pimples are characteristic of inflammatory acne isoniazid, lithium, phenytoin (and other hydantoins), quinine, and are small, prominent, inflamed elevations of the skin.
rifampin, thyroid preparations and trimethadione.
They may rupture to form papules, which are inflammatorylesions appearing as raised, reddened areas on the skin. Pus-tules are small round lesions that are clearly inflamed and TREATMENT
contain visible pus. They may appear red at the base with a Acne usually resolves by the mid 20s. Class 2 to 4 acne may yellowish or whitish center. If the area continues to penetrate produce scarring but this can be minimized if properly treat- into surrounding and underlying tissue and produce necrotic, ed. One of the long-term primary goals in prevention of acne purulent nodular lesions known as cysts, they may lead to pit- is to keep the pilosebaceous ducts open and avoid physical ting and scarring if left untreated.
irritation of the skin and oil-based cosmetics and cleansers.
Scarring is a visible sign of tissue injury and repair when the Nonpharmacologic therapy can include cleansing the skin to tissue cannot be restored to its former state. Scars can be remove excess sebum, minimizing exacerbating factors (tight caused by increased tissue formation and/or by tissue loss.
clothes, irritation, etc.) and not picking or squeezing the They can be of several types, including soft, ice-pick, depressed fibrotic, atrophic macules and follicular macular Only Grade I (noninflammatory) acne is appropriate for self atrophy scars. Some scarring can be treated with topical resur- treatment with higher grades requiring professional care.
facing agents, such as retinol, or microdermabrasion.
Nonpharmacologic measures include cleansing the skin andavoiding factors that contribute to acne. Some topical mildirritants can aid in unblocking pilosebaceous ducts.
ACNE CLASSIFICATION
Inflammatory acne (Grades II through IV) can require both Acne has been classified into the following categories. OTC and Rx products, including oral and topical antibiotics Grade I (Comedonal acne) consists of comedones only; less and retinoids and exfoliants. Often-used active ingredients than about 10 on the face, none on the trunk, no include benzoyl peroxide (2.5 to 10%), salicylic acid (0.5% to scarring and noninflammatory in nature.
2%), sulfur (3% to 8%) and a combination of sulfur (3-8%) with Grade II (Papular acne) is described by 10-25 papules on the either resorcinol (2%) or resorcinol monoacetate (3%), glycol- face and trunk with mild scarring and the presence ic acid, retinoic acid (0.01% to 0.1%) and various antibiotics, of inflammatory lesions, less than 5 mm in such as tetracycline and erythromycin. Dosage forms include solutions, suspensions, sprays, lotions, gels, creams, cleansers, Grade III(Pustular acne) consists of more than 25 pustules Benzoyl peroxide is a local irritant and causes irritation and Grade IV (Severe or persistent pustulocystic acne) consists of desquamation when applied. It prevents closure of the pilose- nodules or cysts with extensive scarring and baceous orifice. It’s irritant action increases the rate of inflammatory lesions over 5 mm in diameter. Also, turnover of the epithelial cells lining the follicular duct and recalcitrant severe cystic acne characterized with increases sloughing. Benzoyl peroxide also is an oxidizing agent and has bactericidal and bacteriostatic action that mayinhibit P. acnes from growing, thus reducing the formation ofirritating free fatty acids. Benzoyl peroxide also has irritant, VARIABLES INVOLVED
There are a number of contributing factors to acne, including Salicylic acid is a mild keratolytic used as a safe and effective environmental, physical, emotional, cosmetic use and heredi- agent in preventing and clearing both comedones and inflam- matory lesions of acne. It increases the rate of desquamation Sulfur is a keratolytic in 3 to 10% concentrations and is gen- Rx - BENZOYL PEROXIDE 10% GEL
erally applied as a thin film one to three times daily. Sulfur preparations do have a noticeable color and odor.
Resorcinol and resorcinol monoacetate in concentrations of Combinations of sulfur and resorcinol act primarily as kera- tolytics, encouraging cell turnover and desquamation.
Glycolic acid (hydroxy acetic acid, hydroxyethanoic acid) is used as an agent to enhance desquamation or peeling of theskin, depending upon the concentration.
Retinoic acid (tretinoin, Vitamin A acid) is a skin irritant. It is 1. Calculate the required quantity of each ingredient for the total used primarily in the treatment of acne vulgaris in which comedones, papules and pustules predominate. It is general- 2. Accurately weigh/measure each ingredient.
ly applied as a cream, gel or alcoholic solution in 3. Dissolve the benzoyl peroxide in the benzyl alcohol.
concentrations ranging from 0.01% to 0.1%. The skin is thor- 4. Add the propylene glycol with rapid mixing; then add the oughly cleansed to remove oiliness about 15-30 minutes prior to application of the tretinoin, once or twice daily.
5. Slowly add about 40 mL of purified water and mix until Tetracycline hydrochloride is a broad spectrum bacteriostat- ic antibiotic that is used topically in concentrations of 0.2% 6. Slowly add the alcohol, followed by the trolamine and mix solution for acne. It is also used orally at a dose of 250 mg twice daily for systemic treatment of acne.
7. Add sufficient purified water to volume and mix well.
Erythromycin is a macrolide antibiotic that is primarily bac- teristatic against a broad range of bacteria. Erythromycin isused orally and topically (2%) in the treatment of severe acne.
Ethyl and isopropyl alcohol are often used as vehicles and A beyond-use date of 6 months can be used for this formulation.7 will evaporate rapidly after application to the skin. Thisresults in a film of the active drug remaining on the skin sur- Rx - ERYTHROMYCIN 2% GEL
Dosage form selection should include those delivery systems that are noncomedogenic. Gels tend to be most effective but some patients may need the less drying lotions or creams for dry or sensitive skin or for use during dry winter weather.
Gels containing only water tend to be slow to dry; the addi- tion of ethyl or isopropyl alcohol to the gel hastens their 1. Calculate the required quantity of each ingredient for the total drying to a film. Gelling agents should not leave a sticky film and should be thin and colorless, thus eliminating the need 2. Accurately weigh/measure each ingredient.
for coloring to blend the product to the color of the skin. Gen- 3. Dissolve the erythromycin in about 70 mL of the ethyl alcohol erally, gels can be recommended for those with darker complexions and creams for those with fair complexions.
4. Add the propylene glycol and mix well.
5. Slowly sprinkle the hydroxypropyl cellulose on to the agitated solution and stir until gelling occurs.
XAMPLES OF COMPOUNDED PREPARATIONS FOR ACNE 6.Add sufficient ethyl alcohol 70% to volume and mix well.
Rx - BENZOYL PEROXIDE 10% CREAM
A beyond-use date of 6 months can be used for this formulation.7 Rx - GLYCOLIC ACID 15% GEL
1. Calculate the required quantity of each ingredient for the 2. Accurately weigh/measure each ingredient.
3. Mix the benzoyl peroxide with the benzyl alcohol.
1. Calculate the required quantity of each ingredient for the total 4. Using low heat, melt the hydrophilic ointment and add the 2. Accurately weigh/measure each ingredient.
5. Add the benzoyl peroxide and benzyl alcohol mixture and 3. Heat about 70 mL of purified water to boiling and add the 6. Cool with stirring, package and label.
4. With agitation, sprinkle on the Methocel E4M Premium and the 5. Cool and incorporate the glycolic acid.
A beyond-use date of 6 months can be used for this formula- 6. Add sufficient purified water to volume and mix well.
4.Dissolve the resorcinol in the anhydrous alcohol (this is A beyond-use date of 6 months can be used for this formu- 5.Add the salicylic acid:lactic acid solution slowly with Rx - SULFUR AND RESORCINOL GEL
6.Add sufficient alcohol USP to volume and mix well.
7.Package in a tight, light-resistant container and label.
A beyond-use date of 6 months can be used for this for- Rx - RESORCINOL 3%, SALICYLIC ACID 2%
& LACTIC ACID 4% PEEL
1.Calculate the required quantity of each ingredient for the 2.Accurately weigh/measure each ingredient.
3. Dissolve the resorcinol in the alcohol and slowly incorporate the carbopol 940 by sprinkling it on with 1. Calculate the required quantity of each ingredient for the 4.Dissolve the trolamine and methylparaben in about 80 2. Accurately weigh/measure each ingredient.
3. Dissolve the resorcinol in the purified water.
5.Combine the two liquids with mixing.
4. Dissolve the salicylic acid in the alcohol, followed by the 6.Make a paste of the sulfur with the propylene glycol and slowly incorporate into the gel and mix well.
7.Add sufficient purified water to volume and mix well.
6. Add sufficient purified water to volume and mix well.
7. Package in an amber container and label.
A beyond-use date of 6 months can be used for this formu- A beyond-use date of 6 months can be used for this for- Rx - RETINOIC ACID 0.2% SOLUTION
INTMENTS
Rx - RETINOIC ACID 0.2% IN PEG OINTMENT
1. Calculate the required quantity of each ingredient for the 2. Accurately weigh/measure each ingredient.
1. Calculate the required quantity of each ingredient for the 3. Dissolve the retinoic acid and the butylated 2.Accurately weigh/measure each ingredient.
4. Add sufficient polyethylene glycol 300 to volume and 3. Dissolve the retinoic acid and the butylated hydroxytoluene in the polyethylene glycol 300.
4.Melt the polyethylene glycol 1540 at about 55º C.
5.Add the retinoic acid and BHT solution to the melted A beyond-use date of 6 months can be used for this for- Rx - TETRACYCLINE HCL 2% TOPICAL SOLUTION
A beyond-use date of 6 months can be used for this formu- OLUTIONS
Rx - JESSNER’S SOLUTION
1. Calculate the required quantity of each ingredient for the 2. Accurately weigh/measure each ingredient.
3. Mix the alcohol USP and the isopropyl alcohol.
4. Dissolve the tetracycline HCl, citric acid and sodium 1. Calculate the required quantity of each ingredient for the 5. Add sufficient purified water to volume and mix well.
2. Accurately weigh/measure each ingredient.
6. Package in a tight, light-resistant container and label.
3. Dissolve the salicylic acid in about 45 mL of the alcohol STABILITYA beyond-use date of 6 months can be used for this for- REFERENCES
1.Spraycar M. Ed. Stedman's Medical Dictionary, 26th ed.
Baltimore, Williams & Wilkins. 1995, p 16.
2.Sluzberger MB and Zaidems SH. Psychogenic factors in dermatological disorders. Medical Clinics of North SUSPENSIONS/LOTIONS
Rx - SULFUR AND SALICYLIC ACID SUSPENSION
3.Somnath P. 17 million persons have acne vulgaris. U.S. 4.Rothman KF, Lucky AW. Acne vulgaris. Adv Dermatol.
5.Gossel TA. OTC anti-acne medications. US Pharm. 6.Hurwitz S. Acne vulgaris: pathogenesis and management. Pediatrics Rev. February 1994;15(2):47-52.
7.US Pharmacopeial Convention, Inc. United States Pharmacopeia 24/National Formulary 19. Rockville, MD: US Pharmacopeial Convention, Inc.; 2001, pp2053- 1. Calculate the required quantity of each ingredient for 2.Accurately weigh/measure each ingredient.
3.Dissolve the methylparaben and the propylparaben in a NOTES__________________________________________
mixture of the propylene glycol and alcohol.
4. Incorporate the sulfur and salicylic acid.
___________________________________________________ 5.Heat about 25 mL of purified water to boiling and slowly sprinkle on the methylcellulose.
___________________________________________________ 6.Add about 25 mL of ice-cold purified water to step #5 ___________________________________________________ 7.Incorporate the mixture from step #4 into the ___________________________________________________ methylcellulose dispersion and mix well.
___________________________________________________ ___________________________________________________ STABILITYA beyond-use date of 6 months can be used for this for- ___________________________________________________ ___________________________________________________ Rx - ZINC SULFIDE COMPOUND LOTION
___________________________________________________ (WHITE LOTION)
___________________________________________________ ___________________________________________________ ___________________________________________________ METHOD OF PREPARATION1.Calculate the required quantity of each ingredient for ___________________________________________________ 2.Accurately weigh/measure each ingredient.
___________________________________________________ 3.Dissolve the zinc sulfate in about 45 mL of purified ___________________________________________________ 4.Dissolve the sulfurated potash in about 45 mL of ___________________________________________________ ___________________________________________________ 6.Slowly and with constant stirring, add the sulfurated ___________________________________________________ potash solution to the zinc sulfate solution.
7.Add sufficient purified water to volume and mix well.
___________________________________________________ ___________________________________________________ STABILITYA beyond-use date of 6 months can be used for this for-mulation.7

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