Pediatric Formulation in the U.S. - Fagron
Pediatric Formulation in the U.S. - Fagron
Pediatric Formulation in the U.S. - Fagron
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Outl<strong>in</strong>e<br />
<strong>Pediatric</strong> <strong>Formulation</strong> <strong>in</strong> <strong>the</strong><br />
U.S.<br />
Loyd V. Allen, Jr., Ph.D.<br />
Editor <strong>in</strong> Chief<br />
International Journal of Pharmaceutical<br />
Compound<strong>in</strong>g<br />
President<br />
International Society of Pharmaceutical<br />
Compound<strong>in</strong>g<br />
I. Introduction<br />
II.<br />
<strong>Pediatric</strong> <strong>Formulation</strong><br />
III.<br />
<strong>Formulation</strong> Considerations<br />
IV.<br />
Compliance Considerations<br />
V. Recommendations<br />
I. Introduction<br />
Role of <strong>the</strong> compound<strong>in</strong>g pharmacist<br />
History of compound<strong>in</strong>g<br />
Reasons for growth of compound<strong>in</strong>g<br />
Special populations<br />
Role of <strong>the</strong><br />
Compound<strong>in</strong>g Pharmacist<br />
“Individualiz<strong>in</strong>g Drug Therapy”<br />
History of Pharmacy<br />
Compound<strong>in</strong>g <strong>in</strong> <strong>the</strong> U.S.<br />
In <strong>the</strong> past, Compound<strong>in</strong>g Was<br />
Pharmacy<br />
1900s gave way to commercially<br />
prepared pharmaceuticals<br />
Many strengths/dosage forms<br />
available<br />
Economics changed all that<br />
Limited strengths/dosage forms<br />
“One Size Fits All” approach<br />
Reasons for <strong>the</strong> Growth of<br />
Pharmacy Compound<strong>in</strong>g<br />
Limited dosage forms<br />
Limited strengths<br />
Home health care<br />
Hospice<br />
Nonavailable drug<br />
products/comb<strong>in</strong>ations<br />
– Discont<strong>in</strong>ued Drugs<br />
– Drug Shortages<br />
Orphan drugs<br />
Veter<strong>in</strong>ary compound<strong>in</strong>g<br />
New <strong>the</strong>rapeutic approaches<br />
Special Patient Populations<br />
1
SPECIAL PATIENT<br />
POPULATIONS<br />
Compounded Lollipops<br />
<strong>Pediatric</strong>s<br />
Geriatrics<br />
Bioidentical Hormone Replacement Therapy<br />
Pa<strong>in</strong> Management<br />
Dental Patients<br />
Environmentally & Cosmetic Sensitive<br />
Sports Injuries<br />
Veter<strong>in</strong>ary Compound<strong>in</strong>g<br />
– Small, Large, Herd, Exotic, Companion<br />
II. <strong>Pediatric</strong> <strong>Formulation</strong>s<br />
Why are <strong>the</strong>y needed?<br />
Why are <strong>the</strong>y needed<br />
Surveys<br />
Problems<br />
Recent Survey<br />
57 hospitals with 36 to 350 licensed<br />
pediatric beds<br />
Need is for >100 liquid formulations for<br />
pediatric patients<br />
Examples of medications not <strong>in</strong> a<br />
suitable dosage form for children<br />
Acetazolamide<br />
Albendazole<br />
Amiodarone<br />
Amitripty<strong>in</strong>e<br />
Arg<strong>in</strong><strong>in</strong>e<br />
Aspartate<br />
Biot<strong>in</strong><br />
Bupropion<br />
Busulfan<br />
Captopril<br />
Carbenicill<strong>in</strong><br />
Cl<strong>in</strong>damyc<strong>in</strong><br />
Clobazam<br />
Clonazepam<br />
Clonid<strong>in</strong>e<br />
Dantrolene<br />
Dexamethasone<br />
Enalapril<br />
Ethambutol<br />
Ethionamide<br />
2
Examples of medications not <strong>in</strong> a<br />
suitable dosage form for children<br />
Famiciclovir<br />
Glutam<strong>in</strong>e<br />
Hydroxyurea<br />
Irbesartan<br />
Lansoprazole<br />
Leucovor<strong>in</strong><br />
Lis<strong>in</strong>opril<br />
Lomust<strong>in</strong>e<br />
Mefloqu<strong>in</strong>e<br />
Methimazole<br />
Methotrexate<br />
Methylphenidate<br />
M<strong>in</strong>oxidil<br />
Neomyc<strong>in</strong><br />
Nicardip<strong>in</strong>e<br />
Nimodip<strong>in</strong>e<br />
Ofloxac<strong>in</strong><br />
Olanzap<strong>in</strong>e<br />
Pancrelipase<br />
Paramomyc<strong>in</strong><br />
Examples of medications not <strong>in</strong> a<br />
suitable dosage form for children<br />
Phenobarbital<br />
Phenoxybenzam<strong>in</strong>e<br />
Prazos<strong>in</strong><br />
Primidone<br />
Probenecid<br />
Procarbaz<strong>in</strong>e<br />
Propafenone<br />
Pyridox<strong>in</strong>e<br />
Riboflav<strong>in</strong><br />
Saqu<strong>in</strong>avir<br />
Scopolam<strong>in</strong>e<br />
Sertral<strong>in</strong>e<br />
Sildenafil<br />
Sodium benzoate<br />
Sotalol<br />
Spironolactone<br />
Testosterone<br />
Tiagab<strong>in</strong>e<br />
Topiramate<br />
Ursodiol<br />
Examples of medications not <strong>in</strong> a<br />
suitable dosage form for children<br />
Verapamil<br />
Vigabatr<strong>in</strong><br />
Warfar<strong>in</strong><br />
Z<strong>in</strong>c sulfate<br />
Government-PHARMA Approaches<br />
Patent extension benefits<br />
Non-compete benefits<br />
Problems to overcome<br />
Patient swallow<strong>in</strong>g<br />
Taste<br />
Odor<br />
Most are “off-label” use<br />
– >75% drugs <strong>in</strong> US not labeled for use <strong>in</strong><br />
children less than 12 yo<br />
Problems with <strong>Pediatric</strong><br />
<strong>Formulation</strong>s<br />
May lack stability studies<br />
May lack bioavailability <strong>in</strong>formation<br />
May lack pk/pd <strong>in</strong>formation<br />
May lack efficacy <strong>in</strong>formation<br />
May lack tolerability <strong>in</strong>formation<br />
3
Drug Product<br />
III. <strong>Formulation</strong><br />
Considerations<br />
Active drug<br />
Excipients<br />
<strong>Formulation</strong> <strong>in</strong>volves<br />
Dosage Forms<br />
Physical<br />
Chemical<br />
Biological<br />
Characteristics of all<br />
<strong>in</strong>gredients <strong>in</strong> <strong>the</strong><br />
formulation<br />
Drops<br />
Syrups<br />
Solutions<br />
Suspensions<br />
Emulsions<br />
Lozenges<br />
Lollipops<br />
Popsicles<br />
Gummy bears<br />
Rapidly dis<strong>in</strong>tegrat<strong>in</strong>g<br />
tablets<br />
Chewable tablets<br />
Capsules (empty<br />
contents)<br />
Suppositories<br />
Injections<br />
Topical/Transdermals<br />
Transdermals<br />
Compounded Gummy<br />
Bears<br />
Source of <strong>Formulation</strong>s<br />
USP<br />
Literature<br />
O<strong>the</strong>r pharmacists/physicians<br />
Develop your own<br />
4
<strong>Formulation</strong> Considerations<br />
Physical properties<br />
Stability (Physical, Chemical, Microbiological)<br />
pKa<br />
pH<br />
Particle size<br />
Hydrous/Anhydrous<br />
Solubility (Presence of water)<br />
Excipient toxicity<br />
Preservatives<br />
Taste/Odor<br />
Preformulation Studies<br />
Microscopic exam<strong>in</strong>ation<br />
Melt<strong>in</strong>g po<strong>in</strong>t depression<br />
Particle size<br />
Polymorphism<br />
Solubility<br />
– Solubility and particle size<br />
– Solubility and pH<br />
Dissolution<br />
Preformulation Studies (Cont’d)<br />
Membrane permeability<br />
Partition coefficient<br />
pKa/Dissociation Constants<br />
Drug and Drug Product Stability<br />
– K<strong>in</strong>etics and Shelf-Life<br />
Preservatives<br />
Aqueous<br />
pH:activity relationship<br />
Taste<br />
Odor<br />
Packag<strong>in</strong>g & Storage<br />
Packag<strong>in</strong>g<br />
Storage<br />
OR<br />
5
Use Commercial Vehicles<br />
Ora-Plus,<br />
Ora-Sweet,<br />
Ora-Sweet SF, Ora-<br />
Blend<br />
Cherry syrup<br />
Methylcellulose 2%:Simple syrup<br />
O<strong>the</strong>rs<br />
IV. Compliance<br />
Considerations<br />
Published studies<br />
Compliance Considerations<br />
Taste<br />
Odor<br />
Palatability<br />
Texture<br />
Color<br />
Sweetness<br />
Viscosity enhancers<br />
Sucrose<br />
Fructose<br />
Stevia<br />
Sorbitol<br />
Glycer<strong>in</strong><br />
Sweeteners<br />
Aspartame<br />
Acesulfame<br />
potassium<br />
Sacchar<strong>in</strong><br />
cyclamate<br />
Flavor<strong>in</strong>g<br />
Colorants<br />
Taste factors<br />
Mask, disguise, enhance, overwhelm<br />
Oil soluble flavors<br />
Water soluble flavors<br />
Liquid vs solid<br />
S<strong>in</strong>gle <strong>in</strong>gredient, multiple <strong>in</strong>gredient,<br />
natural<br />
Color and flavor should match<br />
Lighter shades better than darker<br />
Dyes vs <strong>in</strong>gredients that are colored<br />
6
Recommendations<br />
V. Recommendations<br />
Develop prioritized list of <strong>the</strong> most-needed<br />
formulations<br />
Fund<strong>in</strong>g through Centers of Excellence<br />
and Independent Research<br />
Dissem<strong>in</strong>ation of Data<br />
Monitor<strong>in</strong>g cl<strong>in</strong>ical effectiveness and<br />
tolerability dur<strong>in</strong>g use<br />
Report<strong>in</strong>g mechanism for adverse effects<br />
Compounded Popsicles<br />
Thank You<br />
7
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