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New Compounding Ideas and Marketing Innovation

Ranel A. Larsen, Pharm D, RPh

Erin Michael, MBA, CPhT

Objectives1. Explain common dental conditions encountered by

compounding pharmacists and technicians.2. Discuss the latest compounded treatment options

being prescribed for specific dental conditions.3. Describe formula examples and clinical applications

utilizing various compounded formulations.4. Understand the mechanism of microneedling and the

conditions it can be used for.5. Describe the procedure when using a microneedling

device.6. Explain the different active ingredients used along

with microneedling.

Target Markets

• Dentists

• Dermatologists and Cosmetic Patients

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Compounding for Dental Aliments

Common Dental Conditions

• Oral Mucositis

• Dry Mouth

• Lichen Planus

• TMJ

Mucositis

Inflammation of the mucosal membranes which can cause extreme pain, redness, ulcers and infections.

Most commonly a complication of chemotherapy and/or radiation treatment.

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Mucositis can significantly impact nutritional intake, mouth care and quality of life. Severe cases require a reduction in the chemotherapy dose or a break in the radiation treatment which

can negatively influence prognosis.

Treating Mucositis

• Multinational Association of Supportive Care in Cancer (MASCC) Pain Control Recommendations

– 2% Morphine Mouthwash

– 0.5% Doxepin Mouthwash

– Transdermal Fentanyl

”For compounded preparations such as mouthwashes, there are various formulations that

pharmacists can use based on the experience and needs of the individual physician and patient,

respectively.”

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“Magic Mouthwash”

Common APIs

Anesthetics

Diphen-hydramine

Anti-bacterials

Anti-fungalsSteroids

Misoprostol

Soothing Agents

(Maalox®)

Compounding Pearl - Nystatin

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Commercial Nystatin contains sugar

Sugar Feeds Yeast

Don’t use commercial product – use the raw powder

Compounding Pearl - Nystatin

Compounding Pearl - Ethanol

• The metabolism of ethanol (EtOH) by mucosal and/or bacterial alcohol dehydrogenase generates toxic metabolites such as acetaldehyde and free radicals. – Acetaldehyde accumulation

can damage the oral tissues. It interferes at many sites with DNA synthesis and repair

Make sure your vehicle

doesn’t contain EtOH

Mucositis - Formulas• Stanford Mouthwash

– Tetracycline 12.5mg/ml– Nystatin 12,000 U/ml– Hydrocortisone 0.46mg/ml– Diphenhydramine 1.25mg/ml

• Nystatin 12,500 U/ml / Hydrocortisone 0.25 mg/ml /Diphenhydramine HCl 2.5 mg/ml Mouthwash

• Misoprostol 0.0024%/Diphenhydramine HCl 0.1%/Lidocaine HCl 1% Oral Rinse

• Morphine Sulfate 2% Oral Rinse

• Morphine Sulfate 1mg/ml Oral Suspension

• Doxepin HCl 0.5% Mouthwash

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Dry Mouth (Xerostomia)

Decreased salivary secretions can cause altered taste, difficulty talking and swallowing, and can

lead to dental carries.

Causes of Xerostomia

• Increased Age

• Sjogren’s Syndrome

• Diabetes

• Thyroid Dysfunction

• Dehydration

• Medications

• Chemotherapy/Radiation

Treatment: Pilocarpine

• Cholinergic Agonist– Stimulates secretions of the exocrine glands

• When used orally can have systemic effects– Hyperhidrosis

– Nausea

– Increased urination

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Pilocarpine Formulas

• Pilocarpine HCl 2 mg Troche

• Pilocarpine HCl 10 mg/mL Oral Spray

• Pilocarpine HCl 10 mg/mL Oral Drops

• Pilocarpine HCl 5 mg Lollipop

”provided a significant subjective improvement in speech, swallowing, and decreased

subjective xerostomia as compared to the control”PMID: 26225058

Treatment: Xylitol, Betaine, Olive Oil

Treatment: Xylitol, Betaine, Olive Oil

• Xylitol 7%/Betaine 4%/Olive Oil 2% Oral Rinse– Xylitol: Salivary stimulant

– Betaine: Decreases the loss of water from the mucous component of saliva

– Olive Oil: Lubricant, anti-inflammatory

– Suggested Use: Swish x 1 min and swallow 3-4 x/day

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Treatment: Malic Acid

“The results of our randomized clinical trial clearly show a significant increase of salivary flow rates,

both unstimulated and stimulated, after the treatment with 1% malic acid”

PMID: 22926481

Treatment: Malic Acid

• The dissociation of malic acid generates a stimulation of salivary secretion to dilute the concentration of acids in the oral cavity.

• Malic Acid 1% Oral Spray– Suggested use: 3-4 times a day as needed

Treatment: Electrolytes

• Electrolyte troche or oral saliva gel• Sodium Chloride

• Potassium Chloride

• Calcium Lactate or Calcium Chloride

• Magnesium Sulfate

• Sodium Bicarbonate

• Sodium Phosphate

• Suggested Use: Q 4-6 hours prn

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Treatment: Saliva Substitute• Calcium Phosphate Oral Rinse

– Part A: Calcium Chloride Buffered Solution– Part B: Phosphate Buffer Solution

• Recommended directions for use:– Mix 15 ml of part A and 15 ml of part B together at time

of dose (30 ml total). – Swish the mouth thoroughly for 1 min with 1/2 the soln

and spit out. Repeat with the remaining 1/2 of the solnand spit out.

– Use BID up to 10 times a day as needed– Avoid eating or drinking x 30 min after dose

Oral Lichen Planus

Oral Lichen Planus

• Chronic inflammatory disorder of unknown cause– Appears to be cell-mediated immune

response– Presents with white lines or striae on lateral

borders of tongue, buccal mucosa and gingiva– Atrophic or ulcerative form painful and may

need long term pharmacologic therapy

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Oral Lichen Planus

Common APIs

Steroids

Tretinoin

TacrolimusAnesthetics

Hyaluronic Acid

Treatment: Steroids

• Triamcinolone 0.1% Oral Rinse or Adhesive Paste– Apply up to QID

• Clobetasol 0.05% Oral Rinse– Apply BID for up to 2 weeks

Treatment: Tretinoin

PMID: 20948096

PMID: 453874

Topical Tretinoin 0.05% or 0.1% - Apply BID

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Treatment: Tacrolimus

“It appears that topical tacrolimus is an effective alternative to topical clobetasol and may be

considered as a first-line therapy in the management of Oral Lichen Planus.”

PMID: 26204904

Treatment: Tacrolimus

• Tacrolimus 0.03% Oral Rinse– Suggested Use:

Swish and expectorate ½ tsp BID

– May add steroid or anesthetic if needed

Treatment: Hyaluronic Acid

“Statistically significant improvements were observed in the objective criteria which involved the degree of erythema and

the mean area of the lesions with 0.2% hyaluronic acid application than compared to the control group on placebo.”

PMID: 26894175

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Treatment: Hyaluronic Acid

• Hyaluronic Acid Oral Rinse– Apply TID, avoid eating or drinking for 30 min

after applicationShetty RR, Burde KN, Guttal KS. The Efficacy of Topical Hyaluronic Acid 0.2% in the Management of Symptomatic Oral Lichen

Planus. J Clin Diagn Res. 2016 Jan;10(1):ZC46-50

Treatment: Combination Formulas

• Tretinoin 0.1%/Clobetasol Propionate 0.05%– Oral Rinse

– Oral Paste

• Clobetasol Propionate 0.05%/Lidocaine Hydrochloride 1% Oral Gel

Temporomandibular Disorders(TMJ)

Pain and compromised movement of the jaw joint and the surrounding muscles.

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Treatment: Potassium Complex

“ the authors have found that the gel routinely and predictably provides rapid pain relief and patient

comfort and speeds restoration of the jaw's functional abilities, usually within 5 minutes after it is applied.”

PMID: 18240797

• Potassium Chloride 6%/Potassium Citrate 6%/Potassium Nitrate 6% Topical Gel– Apply to painful areas BID

Treatment: Potassium Complex

TMJ Transdermal Treatment

• Ketoprofen 5%/Cyclobenzaprine HCl 0.5% /Lidocaine HCl 5%/Bupivacaine HCl 1% Topical Cream

• Ketoprofen 10%/Cyclobenzaprine HCl 2% Topical Cream

• Suggested Use: Apply BID-TID

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Marketing Minute

Microneedling

Microneedling is a procedure that uses small, fine needles to create microinjuries in the skin while leaving the epidermis intact

AKA: Percutaneous Collagen Induction or Collagen Induction Therapy

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How does it work?

• Needles break old collagen bundles that tether scars or wrinkles

• This controlled skin injury stimulates the healing cascade and the production of collagen and elastin under the epidermis

Inflammation Proliferation Remodeling

Microneedling increases collagen formation

Control biopsy Biopsy from needled skin 6 weeks post-op; collagen

stained purple

Liebl H, Kloth L. Skin cell proliferation stimulated by microneedles. J Am Coll Clin Wound Spec.2012 Dec 25;4(1):2-6.

Microneedling significantly increases epidermal thickness

Enhanced epidermal thickness after one month and three months of microneedling treatments compared

to baselineEl-Domyati M, Barakat M, Medhat W, et al. Microneedling therapy for atrophic acne scars: an objective evaluation. J Clin Aesthet

Dermatol. 2015 Jul;8(7):36-42.

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Microneedling is used for many cosmetic conditions

Micro-needling

Wrinkles

Scars

Stretch Marks

Large Pores

Skin Rejuv.

Alopecia

Devices UsedRoller Pen

Needle Length • Length of needle selected depends on the

indication of the treatment– 0.2 mm – 0.5 mm: Alopecia and at home skin care

– 0.5 mm – 1 mm: Wrinkles/skin rejuvenation

– 1.5 mm – 2 mm: Scars

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Pain increases as the length/depth of the needle increases

Pre-Procedure Treatment

• Use a topical with:– Vitamin A (retinol)– Vitamin C – Palmitoyl pentapeptide or other peptides

• All of these ensure that collagen production will be maximized and that the skin will heal rapidly

• Use a minimum of 3 weeks before but preferably 3 months before microneedling

Pre-Procedure Formulations

• Retinol Molecular 2%/Ascorbic Acid 5% Topical Serum

• Retinol Molecular 2%/Ascorbic Acid 5% Topical Peptide Cream

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Procedure

1. Clean the skin2. Application of topical anesthetic (Not

necessary for at-home device usage) – Can be applied 2 different ways:

1. Apply 30-60 minutes prior to the start of procedure

OR2. Apply after a light “rolling” with the microneedling

device

Topical Anesthetic Application

• A study demonstrated that after microneedling with 0.5 mm depth and THEN applying Lido 2.5%/Prilo 2.5% pts had better pain control v. topical anesthesia alone when microneedling at a 2.5mm depth was performed.

– El-Fakahany H, Medhat W, Abdallah F, et al. Fractional microneedling: a novel method for enhancement of topical anesthesia before skin aesthetic procedures. Dermatol Surg. 2016 Jan;42(1):50-5.

Formulas:• Benzocaine 20%/Lidocaine 6%/Tetracaine 4% Topical Cream

• Benzocaine 10%/Lidocaine 5%/Tetracaine 2% Topical Cream

Procedure – Cont.

3. Skin is stretched with one hand and rolling is done in multiple directions (horizontal, vertical, and diagonal)

– endpoint is identified as uniform pinpoint bleeding

Singh A, Yadav S. Microneedling: Advances and widening horizons. Indian Dermatol Online J 2016;7:244-54

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Post-Procedure

• Clean face

• Apply serum/topical cream– Optimal time of skin

penetration when using topical products is at 5 minutes as the tissue starts to close considerable after 30 min

– Topical Vitamin A, vitamin C, peptides, hyaluronic acid, etc.

Post Procedure APIsAPI ↓

RednessMoisturizer Anti-

InflammatoryAids in healing

Anti-Wrinkle

Simulates collagen

production

Anti-Oxidant

Beta-glucan(Up to 2%)

X X X

Hyaluronic Acid(0.5-2%)

X X X

Niacinamide(Up to 6%)

X X X

Vitamin A(Retinol)(Up to 5%)

X X

Vitamin C(up to 15%)

X X

Post Procedure FormulationsGels: • Sodium Hyaluronate 1% Gel• Sodium Hyaluronate 2% Gel• Retinol Molecular 1%/Hyaluronic Acid Topical Gel

Serums: • Niacinamide 5%/Ascorbic Acid 2.5% Topical Serum• Ascorbic Acid 5%/Sodium Hyaluronate Topical

Serum• Ascorbic Acid 10%/Sodium Hyaluronate Topical

Serum

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Post Procedure Formulations

Creams:• Ascorbic Acid 5%/Beta Glucan/Hyaluronic Acid

Topical Peptide Cream

• Niacinamide 5%/Hyaluronic Acid/Beta GlucanTopical Peptide Cream

• Niacinamide 5%/Retinol Molecular 1%/Hyaluronic Acid/Beta Glucan Topical Peptide Cream

Recovery

• Quick recovery due to epidermis remaining intact

• Minimal side effects– Mild redness– Irritation– Inflammation

• Side effects typically dissipate over 24-48 hours

Counseling Points

• Counsel patient to avoid sun exposure and use sunscreen

• Apply serum/cream daily

• Repeat treatment usually at one month intervals x 4-6 treatments

• Takes approximately 3-6 months for final results.

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Contraindications

1. Active acne

2. Herpes labialis or any other local infection

3. Moderate – severe chronic skin conditions (eczema/psoriasis)

4. Patients on anticoagulant therapy

5. Extreme keloidal tendency

6. Patients on chemotherapy/radiation

Results – Fine Lines/Wrinkles

Before After 1 treatment

Fernandes, D. Minimally invasive percutaneous collagen induction. Oral Maxillofac Surg Clin North Am. 2005 Feb;17(1):51-63.

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Results – Acne Scars/Hyperpigmentation

Before After 3 treatmentsLiebl H, Kloth L. Skin cell proliferation stimulated by microneedles. J Am Coll Clin Wound

Spec.2012 Dec 25;4(1):2-6.

Results – Androgenic Alopecia

Pre treatment -Baseline

Post treatment 12 weeks Weekly microneedling +

1ml 5% minoxidil BID

Dhurat R, Sukesh MS, Avhad G, et al. A randomized evaluator blinded study of effect of microneedling in androgenetic alopecia: a pilot study. Int J Trichology. 2013 Jan-Mar, 5(1): 6-11.

Androgenic Alopecia Formulations

• Minoxidil 5% / Azelaic Acid 5% Topical Foam

• Minoxidil 10% / Finasteride 0.1%Topical Gel

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How can microneedling help my practice?• At home microneedling devices can help increase

effectiveness of your formulations

• Dispense with cosmetics/anti-aging/firming formulation

• Many BHRT patients are interested in anti-aging

Are you ready to get started?

Marketing Minute

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References• Sroussi HY, Epstein JB, Bensadoun RJ, saunders DP, et al. Common oral

complications of head and neck cancer radiation therapy: mucositis, infections, saliva change, fibrosis, sensory dysfunctions, dental caries, periodontal disease, and osteoradionecrosis. Cancer Med. 2017 Dec;6(12):2918-31.

• Lalla RV, Sonis ST, Peterson DE. Management of oral mucositis in patients with cancer. Dent Clin North Am. 2008 Jan;52(1):61-77, viii.

• Lalla RV, Bowen J, Barasch A, Elting L, et al. MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer. 2014 May 15;120(10):1453-61.

• Cerchietti LC, Navigante AH, Bonomi MR, Zaderajko MA, et al. Effect of topical morphine for mucositis-associated pain following concomitant chemoradiotherapy for head and neck carcinoma. Cancer. 2002 Nov 15;95(10):2230-6

• Pöschl, G., Seitz, H.K., 2004. Alcohol and cancer. Alcohol Alcohol. 39, 155–165, OxfOxfs.

• Kuntz R, Allen M, Osburn J. Xerostomia. Int J Pharm Compd. 2000 May-Jun;4(3):176-7.

• Gil-Montoya JA, Silvestre FJ, Barrios R, Silbestre-Rangil J. Treatment of xerostomia and hyposalivation in the elderly: A systematic review. Med Oral Patol Oral Cir Bucal. 2016 May 1;21(3):e355-66.

References• Chiang YZ, Al-Niaimi F, Madan V. Comparative efficacy and patient preference

of topical anesthetics in dermatological laser treatments and skin microneedling. J Cutan Aesthet Surg. 2015 Jul-Sep;8(3):143-6.

• Cohen BE, Elbuluk N. Microneedling in skin of color: a review of uses and efficacy. J Am Acad Dermatol. 2016 Feb;74(2):348-55.

• Singh A, Yadav S. Microneedling: Advances and widening horizons. Indian Dermatol Online J 2016;7:244-54

• El-Domyati M, Barakat M, Medhat W, et al. Microneedling therapy for atrophic acne scars: an objective evaluation. J Clin Aesthet Dermatol. 2015 Jul;8(7):36-42.

• Camirand A, Doucet J. Needle dermabrasion. Aesthetic Plast Surg. 1997 Jan-Feb;21(1):48-51.

• Few J, Semersky A. Commentary on: micro-needling depth penetration, presence of pigment particles, and fluorescein-stained platelets: clinical usage for aesthetic concerns. Aesthet Surg J. 2016 Aug 16.

• Fernandes, D. Minimally invasive percutaneous collagen induction. Oral Maxillofac Surg Clin North Am. 2005 Feb;17(1):51-63.

References• Liebl H, Kloth L. Skin cell proliferation stimulated by microneedles. J

Am Coll Clin Wound Spec. 2012 Dec 25;4(1):2-6. • Dhurat R, Sukesh MS, Avhad G, et al. A randomized evaluator

blinded study of effect of microneedling in androgenetic alopecia: a pilot study. Int J Trichology. 2013 Jan-Mar, 5(1): 6-11.

• Chawla S. Split face comparative study of microneedling with PRP versus microneedling with vitamin C in treating atrophic post acne scars. J Cutan Aesthet Surg. 2014 Oct-Dec; 7(4): 209-212.

• Doddaballapur S. Microneedling with dermaroller. J Cutan Aesthet Surg. 2009; 2: 110-111.

• Gehring W. Nicotinic acid/niacinamide and the skin. Cosmet Dermatol. 2004 Apr;3(2):88-93.

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Thank you!