Compounding Options in Women s Health: Dosage Forms

Compounding Options in Women s Health: Dosage Forms Ranel A. Larsen, RPh, PharmD HRT Symposium Las Vegas, NV February 16 18, 2017

Routes of Administration Common: Topical Oral Sublingual Vaginal Other: Injection Pellets Topical Steroids (hormones) are low molecular weight, highly lipophilic molecules Use of a true transdermal base (like those used in pain management) is not required for absorption Topical HRT Application Considerations Site of application Common: Inside of forearm, back of upper arm, upper thigh Avoid transference: back of knee, buttocks, top of foot Rub in for at least two minutes Rotate sites Counsel on transference 2017 PCCA. All Rights Reserved. 1

Topical Bases Used for HRT Creams VersaBase Cream Cosmetic HRT Emollient Cream NataCream Gels VersaBase Gel HEC, HPC, carbopol (carbomer) VersaBase / Progesterone Base Study PCCA Document #97711 BUD Formulas - Example PCCA Formula #12114 Progesterone 10mg/gm to 100mg/gm Topical Cream (VersaBase ) BUD Bracketed Study BUD = 180 days Search for BUD in formula search 2017 PCCA. All Rights Reserved. 2

Common Topical Formulas PCCA Formula #12116 Estriol / Estradiol [50%/50%] 0.25mg/0.5Gm to 1mg/0.5Gm Topical Cream (VersaBase ) (FormulaPlus BUD Bracketed Study) PCCA Formula #12023 Estriol / Estradiol [80%/20%] 0.5mg/0.5Gm Topical Cream (VersaBase ) PCCA Formula #12019 Estriol / Estradiol [50%/50%] 0.5mg/0.5Gm / Progesterone 25mg/0.5Gm Topical Cream (VersaBase ) PCCA Formula #12099 Estriol / Estradiol [80%/20%] 1mg/Gm / Testosterone 1mg/Gm Topical Cream (VersaBase ) PCCA Formula #9285 Testosterone 2mg/mL Topical Cream (VersaBase ) Topical Administration Dispensing Device Considerations Accurate measurement of dosage (1ml vs. 1Gm) Ability to adjust dosage Prevent contamination Dispensing options Metered devices (pumps, topi clicks) Syringes Jars and tubes with adapters MegaPumps PCCA Document #98451 Range of sizes Easy to fill and use Precise 2017 PCCA. All Rights Reserved. 3

Topi-Click PCCA Document #99258 Accurate 0.25ml/click Topical and vaginal devices Requires more instruction to use Calibrating your device Determine how much compound is dispensed with each actuation. See PCCA Document #97959 and #98747 for details or call the Pharmacy Consulting Department. Oral Dosage Forms Immediate release capsules Slow release capsules Oil filled capsules Sublingual / buccal 2017 PCCA. All Rights Reserved. 4

Oral Dosage Forms General Considerations Micronized vs. non micronized Use source of chemical with consistent quality Size and % of micronization is critical Higher risk of toxic metabolites with oral dosing of estrogens Immediate-release Capsules 95% destroyed in the upper GI tract Requires more frequent dosing No good reason to use Slow-release Capsules Provides good level response Less failures and side effects from peak and valley effects of other dosage forms Can dose QD or BID Commonly used for progesterone When prescribing write E4M on prescription PCCA Document #97577 2017 PCCA. All Rights Reserved. 5

Oil-filled Capsules Absorption through lymphatic system bypasses GI destruction and first pass effect to some degree NOT sustained release May have to dose BID QID More time consuming to compound LoxOral - So Much More Than A Filler! Ease of use: Reduces static (progesterone) Reduce clumping Improves flowability Improved dissolution: enhances the release of APIs potentially leading to improved absorption. 2017 PCCA. All Rights Reserved. 6

Common Oral Formulas PCCA Formula #10800 Progesterone 50mg Slow Release Cap (LoxOral ) PCCA Formula # 10797 Progesterone 100mg Slow Release Cap (LoxOral ) PCCA Formula # 6115 Progesterone 150mg Slow Release Cap PCCA Formula # 8093 DHEA 5mg Slow Release Cap PCCA Formula # 6867 Progesterone 100mg Oil Cap Sublingual/Buccal Rapid dissolve tablets (RDTs) Troches Drops Sublingual/Buccal Advantages Avoids upper GI tract destruction Avoids 1 st pass effect Fast dissolution Quick onset Disadvantages May have to dose more often Taste may be unacceptable Conflicts with saliva testing Some patients chew and swallow = IR and not SL 2017 PCCA. All Rights Reserved. 7

Rapid Dissolve Tablets Developed to be an oral dosage form but for hormones it is used as a sublingual Progesterone is most common Taste can be a problem Try to allow it to dissolve instead of chewing Good flavor choices Melting point of actives RDT-Plus Anhydrous Requires baking: 15 minutes at 110 C OR 30 minutes at 80 C Sugar free PCCA Document #99284 Troches (Lozenges) Gelatin Masks bitter tastes better Dissolves in 5 10 minutes Soft consistency Stability contains water Can use molds to make into gummies PEG (Base A, Polyglycol) Masks bitter tastes less Dissolves in 10 20 minutes Harder consistency Stability better (anhydrous) Can make small mini type troches with tablet triturate molds 2017 PCCA. All Rights Reserved. 8

Sublingual Drops Prescribe in a specific volume vs. drops to be accurate Vehicle choices Alcohol / glycerin mixtures (PCCA Formula #4574) Oils (PCCA Formula #9273) Concentration Flavor vs. convenience Should use small volume, 0.2 0.25ml max Concentrated taste harder to mask Common Sublingual Formulas PCCA Formula #12387 Progesterone 50mg Rapid Dissolve Tablet (RDT Plus ) PCCA Formula #12389 Progesterone 100mg Rapid Dissolve Tablet (RDT Plus ) PCCA Formula #11303 Estriol / Estradiol [80%/20%] 1mg / Progesterone 100mg Polyglycol Troche PCCA Formula #5897 Progesterone 100mg Polyglycol Troche Base PCCA Formula #3731 Progesterone 100mg/mL Oil Sublingual Suspension PCCA Formula #7787 DHEA 10mg/mL Sublingual Drops Vaginal Administration Dosage forms Suppositories Creams Gels Troches Capsules 2017 PCCA. All Rights Reserved. 9

Vaginal Administration Good absorption systemically Used for systemic and local effects Documented effectiveness for Progesterone in luteal phase defect Commercial products for Estrogens Suppository Bases Base MBK Non irritating Melts quickly at body temp Fatty base Contains an emulsifier that allows oil soluble drugs to release more readily Base A (PEG) Can irritate more than MBK Dissolves vs. melts Polyethylene glycol base More gradual drug release Counsel patient to dip in water prior to insertion Common Suppository Formulas PCCA Formula #7218 Progesterone 100mg Base MBK Suppository (Pink Mold) (FormulaPlus BUD Study) PCCA Formula #9994 Estriol 0.5mg Base MBK Vaginal Suppository (Medium Shell Mold) PCCA Formula #9899 DHEA 6.5mg Base MBK Vaginal Suppository (Pink Mold) 2017 PCCA. All Rights Reserved. 10

Common Suppository Formulas (cont d) PCCA Formula #1329 Boric Acid 600mg Base MBK Vaginal Suppository (Pink Mold) PCCA Formula #9910 Hyaluronic Acid Sodium 5mg Compound Base MBK Vaginal Suppository (Medium Shell Mold) PCCA Formula #12289 Coconut Oil Suppository, General Formula (Medium Shell Mold) Considerations in Vaginal Creams / Gels Preservatives Petrolatum free Hypoallergenic Wetting agents Volume to be inserted ph Topical Bases Chart PCCA Document #97305 Lists different bases with specific information: Description Vaginal use ph Preservatives Other related documents 2017 PCCA. All Rights Reserved. 11

MucoLox Mucoadhesive polymers that provides longlasting coverage and increases contact time with API Ionic attraction creates bond with the mucous membrane Won t easily wash away with vaginal discharge or other mucosal secretions MucoLox PCCA Document #98930 Compounded medicines prepared with MucoLox are then likely to remain at the site of action for a long period of time without causing damage to the vaginal tissue, potentially reducing the need for frequent dosing and increasing the effectiveness of each dose administration. Common Vaginal Cream / Gel Formulas PCCA Formula # 12033 Estriol 0.05% Vaginal Gel (MucoLox / VersaBase ) PCCA Formula # 11116 Estriol 0.1% / Testosterone 0.1% Vaginal Gel (MucoLox / VersaBase ) (FormulaPlus BUD Study) PCCA Formula # 11946 Progesterone 10% Vaginal Gel (MucoLox / VersaBase ) PCCA Formula # 11386 DHEA 13mg/Gm Vaginal Gel (MucoLox / VersaBase ) 2017 PCCA. All Rights Reserved. 12

Common Vaginal Cream / Gel Formulas (cont d) PCCA Formula # 11117 Sodium Hyaluronate 5mg/Gm Compound Vaginal Gel (MucoLox / VersaBase ) PCCA Formula # 6991 Amitriptyline HCl 2% / Baclofen 2% Vaginal Cream PCCA Formula # 11109 Ketamine HCl 0.5% / Diazepam 1% / Baclofen 2% Vaginal Gel (MucoLox / VersaBase ) Vaginal Troche Bases to use: MBK or polyglycol Size depends on mold used and strength that needs to be delivered PCCA Formula #9796 MBK Troche, General Formula PCCA Formula #9363 Polyglycol Troche, General Formula (Tablet Triturate 100mg Mold) Calibrate your mold with your base Vaginal Capsule MCC, LoxOral or acidophilus as filler Do not use lactose as a filler Good alternative to suppository, not as much leakage Formulas: PCCA Formula #5658 Boric Acid 600mg Vaginal Capsules Size #0 PCCA Formula #10796 Progesterone100 mg Capsules Size #1 (LoxOral ) 2017 PCCA. All Rights Reserved. 13

Injections High supraphysiologic doses given High level initially followed by drop off until next dose Convenient? Given much less often Administered in doctor s office Compounded products Oil or aqueous suspensions Different salts / esters have different durations Pellets Pros Convenience Cons Invasive procedure Cannot adjust dosing Higher than normal doses Patient often feels bad when dose wears off Cost to patient Sterility? PCCA Document #98574 Thinking Outside the Box... Vaginal RDT RDT Plus (sugar free) Does dryness change dissolution time? Coconut oil vaginal capsules 2017 PCCA. All Rights Reserved. 14

Questions? 2017 PCCA. All Rights Reserved. 15