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Compounding

First published in the Australian Journal of Pharmacy online version. 1st September 2018. Reproduced and distributed by the Medisca Group of companies with the permission of the publisher.

Compounding: what was it… when, why, and what is it today?

By: Rebecca O’Grady and Patricia Ullmann

AFTER COMPLETING THIS The act of combining ingredients into medicinal ACTIVITY, PHARMACISTS SHOULD BE ABLE TO: preparations has existed long before the term compounding. The processes of pharmacy can be dated 1. Discuss situations where as far back as 3000 BC2 ; with the first documented compounding is appropriate processes of pharmacy linked back to ancient 2. Describe examples of 2 compounded products civilisations of Egypt, Rome, and Greece. used in the treatment of various conditions where n early example is the use and trees into pastes to be applied commercially available of the bark and leaves from topically or taken orally.36 The products were inappropriate the willow tree. Patients use of the willow bark, led to the for the patient. Awould chew on the bark or drink discovery of acetyl salicylic acid 3. Describe the difference tea from willow tree leaves (aspirin) which is derived from between simple and complex which had been brewed.35 The willow.36 compounding. ancient Egyptians used the leaves from the willow tree to reduce Over the centuries, an apothecary The 2010 Competency Standards inflammation of wounds and was a medical professional addressed by this activity joints, to decrease pain associated who formulated and dispensed include: 1.1, 1.2, 1.3, 1.4, 4.1, with these conditions.36 Early medications to patients, physicians 4.2, 5.1, 5.2. pharmacists compounded the and surgeons.2 Various editions components of the herbs, flowers of the Australian Pharmaceutical The 2016 Competency Standards Formulary (APF) include numerous addressed by this activity the australian extemporaneous preparation include: 1.1, 1.2, 1.3, 1.5, 2.1, college of pharmacy formulas which are referred 3.2, 3.4.

1 Compounding

Figure 1: Timeline of the history and evolution of compounding3 to by pharmacists even today. (SNPs).21, 37 This can then be used This definition of compounding is Technological progress gave rise to predict a patient’s response to divided into Simple and Complex to the use of mass manufactured different medications.37 Physicians compounding: pharmaceuticals, thereby who follow the Walsh Protocol diminishing the prescribing of for nutraceutical therapy, often Simple compounding uses compounded medications. The use genetic testing to adjust the formulations for which information 21st Century has seen a shift medications to suit each patient’s confirming quality, stability, safety, towards customised (compounded) biochemistry requirements.40 efficacy and rationality is available. medications. This may be the preparation Today compounding, or of formulations published in The shift back towards extemporaneous dispensing, is the reputable sources such as the compounded medications practice of preparing a customised Australian Pharmaceutical has come about as awareness medication to suit a particular Formulary and Handbook9 (APF). increased that the “one size fits all” patient need. In Guidelines on However, not all APF formulations approach of mass manufactured Compounding of Medicines, The fall under Simple compounding - medications is not appropriate Pharmacy Board of Australia for example preparations requiring for all patients. The importance of defines compounding as “the to be compounded under sterile pharmacogenomics has increased extemporaneous preparation and conditions.1 over the past few decades.21 supply of a single ‘unit of issue’ of In nutraceutical therapy, basic a therapeutic product intended Complex compounding is the genetic and molecular profiling for supply for a specific patient in preparation and supply of a single is conducted to map a patients’ response to an identified need”.1 ‘unit of issue’ of a therapeutic single nucleotide polymorphisms product that is intended for supply

2 Compounding for a specific patient, that requires unsuitable (e.g. if a patient model is also a key component of or involves special competencies, experienced an allergy to an Professional Practice Standards38, equipment, processes, or facilities. excipient in the commercial specifically Standard 5 and the risk Examples of complex compounded product), or management tool of Appendix 7: products are sterile preparations, • when undertaking research Compounding decision support preparations containing sanctioned by a recognised and risk assessment tool. ingredients posing an occupational human research ethics health and safety hazard such as committee. In May 2018, the Pharmacy Council cytotoxic or hormones, micro-dose of New South Wales (PCNSW) single unit dosage forms containing Compounded preparations are not released a fact sheet on “Raw less than 25 mg (or up to 25 per exempt from, and are still required materials used in compounding” cent by weight or volume) of to meet, the quality standards laid which aims to provide guidance to active ingredient, and sustained out in the Therapeutic Goods Act pharmacists when sourcing the release or other modified-release of 1989.1 Quality assurance of all raw materials to be used in the preparations. 1 compounded preparations will compounding process- both active need to be conducted, referring to pharmaceutical ingredients (APIs) Compounding allows patients the procedures and processes put and non-active pharmaceutical access to treatments options, in place by the pharmacy to ensure ingredients.4 The “acceptable” which are suited to their a high quality preparation and materials are procured from requirements, to facilitate patient safety. As per the APF, this Australian manufacturers who improved therapeutic outcomes includes:9 hold an “appropriate TGA licence for patients, with a decrease in to manufacture” and provide a adverse effects.21 For example, the • appropriately-trained compe- “genuine Certificate of Analysis”. commercial product (meaning the tent staff A manufacturer is defined as one proprietary product registered or • quality ingredients from ap- involved in “any or all steps in the listed on the Australian Register proved sources manufacturing process including of Therapeutic Goods) is only • reproducible formulations packaging, labelling etc”. “Search manufactured in dosage forms • standard operating procedures Australian Manufacturers at www. and/or strengths which are (SOPs) for all processes ebs.tga.gov.au and/or speak to the unsuitable for a specific patient; involved in the compounding, manufacturer”.4 or the commercial product including cleaning, has been withdrawn from the equipment, storage, handling, Ingredients sourced from a market for financial reasons; or documentation distributor of raw material holding the commercial product uses • suitable equipment and solely a wholesale licence issued excipients to which a specific facilities appropriately by a State health department patient is intolerant. This is aligned maintained. do not fall in the “acceptable” with the concept of “the right drug category. Further information on at the right time via the right route When deciding to compound the manufacturer is to be provided for the right patient.”22 a medication, pharmacists are or further third party testing in additionally required to conduct Australia is to be conducted on the As per Pharmacy Board of a risk assessment to determine product. The Fact Sheet provides Australia’s Guidelines on the appropriateness of the a Manufacturer assessment compounding of medicines 1, there compounded preparation for the flowchart⁴ to guide raw material are three circumstances when specific patient. The Guidelines procurement decisions. compounding a medication may be on compounding of medicines considered: require evidence of safety, stability, In addition to PCNSW’s fact and efficacy for a prescription sheet “Raw materials used in • an appropriate commercial before it is compounded, to ensure compounding”, pharmacists product is unavailable high quality patient-centred may refer to Section A of the • a commercial product is care. The patient-centred care current edition of the Australian 3 Compounding Table 1: Examples of different non-sterile compounded dosage forms. 8 compounded capsules.8 These machines are commonly avail- State-of-matter able in 100 and 300 Aromatic waters units. Partial fill kits are avail- Foams able which block off sections of the machine allowing a smaller Linctuses number of capsules to be filled. Mixtures The machine is loaded with capsules and the caps removed from the base of the capsule. The compounder then pro- ceeds to spread and tamp the homogenously mixed Medication stick into the capsules until all the Troche is in the capsules. The Semi-solid capsules are then re assembled with the caps being replaced, Paste and the capsules are locked. Ointment Amongst other quality valida- tion procedures, a sample of the capsules should then be Solid Capsule weighed individually to ensure even filling.8 Rapid dissolving 2. Capsules can also be filled by hand using the “punch” Pharmaceutical Formulary and available in a variety of sizes which method7 whereby the powders 9 Handbook Extemporaneous. hold different volumes. The smaller are triturated and mixed by Risk management needs to the capsule size number, the larger geometric dilution to form be undertaken which involves the volume. For example, a size a homogenous mixture. The identification, assessment, and 0 capsule holds a larger volume capsule base is then “punched” mitigation of risk. These processes (0.68 mL) than a size 3 capsule (0.3 into the powder, filling the are a part of quality use of mL). The capsule size needs to be capsule until it contains the medicines to ensure high quality, chosen based on the volume of correct weight. 7 safe, effective treatment options the powder dosage as well as the for patients, and are also required intended patient. The aim is to When compounding capsules, in Pharmaceuticals Society of use the smallest volume capsule the compounder will find that the Australia’s, Professional Practice possible to fit the whole dosage entire volume of the capsule will 38 Standards. prescribed, as well as the patient not be filled by the dosage of the requirements. The most commonly prescribed API. The remaining Compounding provides access to compounded capsules are those volume will need to be filled with the preparation of various dosage that contain (powders). an excipient, often referred to forms. Pharmacists, and technicians as a filler. Commonly used fillers working under pharmacists’ in capsule compounds include Capsules supervision, can prepare and proprietary capsule filling blends, Capsules are solid dosage forms fill compounded powder filled microcrystalline cellulose, lactose, that can contain solids, semi solids, capsules using various methods: hypromellose and mannitol. or in a hard or soft shell. The filler used needs to be These shells are most commonly 1. Capsules can be filled using a appropriately chosen to suit the composed of gelatine, but can also capsule machine, which is the API and the intended method be composed of cellulose, and are most common method of filling of delivery. Refer to Ullmann P., 4 Compounding

Commonly used fillers in capsule compounds include proprietary capsule filling blends, microcrystalline cellulose, lactose, hypromellose and mannitol.

Australian Journal of Pharmacy, right?” for details. These were developed to enhance Vol. 98, No.1164, August 2017, A compounder may compound absorption, protect against pp.78-83 “Excipient selection for a capsule when a commercial hygroscopicity, and improve compounded pharmaceutical product has been removed from dissolution rates of the APIs.31 capsules: they’re only fillers, the market for reasons other than right?” for details. safety or efficacy. An example Creams of this scenario includes the Creams are preparations intended A compounder may compound a commercial product Cafergot™ for application to the skin or the capsule when a commercial prod- (currently not available in mucous membranes such as the uct has been removed from the Australia) which is a migraine vagina and the rectum. Cream market for reasons other than treatment containing caffeine bases may be compounded as safety or efficacy. An example of and ergotamine. A physician may either oily creams or aqueous this scenario includes the commer- prescribe a compounded version creams. When determining cial product Cafergot™ (currently of these capsules in a case where which cream base to use in the not available in Australia) which is the current commercially available preparation, the compounder a migraine treatment containing migraine treatments have proven considers several determinants; caffeine and ergotamine. A physi- to be unsuitable for a patient. the physiochemical properties cian may prescribe a compounded of the API, the physiochemical version of these capsules in a case An example of when a properties of the base, the where the current commercially compounder can prepare a intended site of application, and available migraine treatments dosage form when there is no the intended method of delivery have proven to be unsuitable for a commercial product available (topical vs ). patient. is dehydroepiandrosterone (DHEA) capsules. These capsules Once a patient has tried the When compounding capsules, are compounded for patients commercially available treatment the compounder will find that the being treated for premature options without sufficient relief entire volume of the capsule will ovarian failure.23 Currently of their symptoms, a physician not be filled by the dosage of the there is no commercial product may decide to treat a patient who prescribed API. The remaining pharmaceutical (non-homeopathic) presents with chronic anal fissures volume will need to be filled with DHEA available on the Australian with a 2% diltiazem cream.20 an excipient, often referred to market. This will need to be prepared in as a filler. Commonly used fillers a cream base suitable for rectal in capsule compounds include Lactose is a commonly used filler application by a compounding proprietary capsule filling blends, in a variety of the commercially pharmacy.20 microcrystalline cellulose, lactose, available capsule products. There hypromellose and mannitol. are a number of patients who are Another example is Bactroban™, a The filler used needs to be unable to tolerate lactose due to commonly used topical antibiotic appropriately chosen to suit the medical conditions. Compounders product, which contains 2% API and the intended method may be able to compound a mupirocin as mupirocin calcium. of delivery. Refer to Ullmann P., treatment option for these For a long period of time in 2017, Australian Journal of Pharmacy, patients using a filler other than this commercial product was out of Vol. 98, No.1164, August 2017, lactose that suits the API they are stock from the manufacturer. After pp.78-83 “Excipient selection for incorporating. There are a number consultation with the physician, compounded pharmaceutical of lactose-free proprietary capsule to determine that there were capsules: they’re only fillers, filler powder blends on the market. no other therapeutic treatment

5 Compounding

Compounding of topical preparations for local or transdermal effect may reduce the risk of systemic adverse events.39 options for patients, compounding mL per actuation. This facilitates 10% diclofenac has been pharmacists were able to prepare convenient application to the cats’ found to be efficacious for the this preparation. To confirm stock ear and accurate dosing. reduction of pain associated with availability of commercial products inflammation.10 This is a viable compounders are able to check the treatment option for this patient “Medicine Shortages Information A gel is a semi solid preparation offering an alternative dosage Initiative” webpage on the which consist of suspensions route of the NSAID which has Therapeutic Goods Administration made up of either, small decreased systemic side effects.11 website, or may confirm with inorganic particles or large pharmaceutical wholesalers and organic molecules, which are When a teenage patient suffering the manufacturers. interpenetrated by a liquid.5 from moderate acne vulgaris Gels can be utilised in several has been treated with all over- Compounding of topical routes of administration including the- counter commercial acne preparations for local or oral, topical, transdermal, preparations without relief of transdermal effect may reduce the intranasal, vaginal and rectal.14 their symptoms, the physician may risk of systemic adverse events.39 Gel bases can be divided into prescribe the commercial topical For example, patients experiencing several classifications including clindamycin products. Where there neuropathic pain after a shingles inorganic, organic, hydrogels, is a need to avoid the systemic infection may be prescribed oral and organogels.14 The gel base adverse events associated with gabapentin capsules for pain chosen will depend on the route the oral treatments the use of a management. However, in some of delivery required for the API. topical compounded treatment cases, the adverse reactions Similarly to creams, compounders supported by evidence of safety, experienced by patients has led may purchase pre-made efficacy and stability, such as a to the cessation of treatment. proprietary gel bases, or may topical niacinamide 4% gel, may be Their physician may take a topical compound a gel base from raw compounded.30 approach to treat the neuropathic ingredients. pain using compounded topical Eosinophilic oesophagitis is a gabapentin24 in order to reduce When would a compounder need painful inflammatory condition potential gastrointestinal adverse to prepare a gel preparation? of the oesophagitis caused by reactions. A patient with severe chronic inhaled or ingested allergens. Achilles tendon pain, and a history Given the nature and the Veterinary patients also benefit of gastrointestinal (GI) issues, has target site of the disease, it has from compounded treatment tried all the available topical pain proven difficult to treat with the options. Cats are commonly known relief creams without reduction commercially available products. to suffer from hypothyroidism, in their pain symptoms. The Compounding pharmacists may however, administering oral physician may collaborate with prepare a Budesonide 1 mg/mL medication can be challenging. the compounding pharmacist oral oesophageal gel using pluronic Compounding pharmacists in determining the treatment gel 20% as the base.32 Patients may prepare a transdermal options. Given the patient’s history are then able to swallow this methimazole 5 mg/ 0.1 mL of GI issues, oral medication would preparation which will coat the pluronic lecithin organogel (PLO) not be appropriate; however, oesophagus to provide relief. to be applied to the pinna.25 This options of a compounded high- preparation can be dispensed in strength topical non-steroidal Ointments and pastes are prepared a metered dosed device anti-inflammatory (NSAID) for the following reasons: 16 that accurately dispenses 0.1 may be considered. Topical 6 Compounding

Oral liquids may need to be compounded in order to increase patient compliance to improve therapeutic outcomes.

• Protection of the skin from the patients who have difficulty paediatric patients are unable to environment swallowing solid dosage forms. swallow the commercially available • Hydration of the skin These preparations include products. When the physician • Topical or systemic delivery of aromatic waters, , linctuses, decides to have a compounded oral APIs. mixtures, solutions, suspensions liquid prepared for their patient, and syrups. Oral liquids may need the compounder needs to assess A number of features determine to be compounded in order to the chemical and physical stabilities the amount of drug that will increase patient compliance to of the omeprazole when it is in a penetrate into the skin from an improve therapeutic outcomes. liquid dosage form. Omeprazole ointment or paste. These include Oral liquid preparations are has a narrow pH of stability. This surface area, condition of the susceptible to chemical, physical, is an alkaline pH with a maximum skin, pressure applied, the base and microbial instability. The pH of stability of 11 and rapid used, and if an occlusive dressing characteristics of the API such decomposition below a pH of is used or not.16 When choosing as solubility in various solvents/ 7.8.9, 15 The formulation needs an ointment base a number of co-solvents, pH of stability, pH to include an alkaliniser, such as factors needs to be considered. of solubility, risk of hydrolysis, sodium hydroxide, to increase the This includes drug specific factors oxidation, and chelation, and risk pH. This ensures the omeprazole such as stability of the API in the of microbial proliferation need be will be within the pH of stability base, and also if the API will be considered. Even palatability of range; or the compounder may bioavailable in the base chosen.17 these preparations is an important use a commercially manufactured factor to be considered, as taste alkaline pH buffered base. A commonly compounded affects patient compliance. Various Another compounded oral liquid ointment preparation is a salicylic flavours and sweeteners may formulation is melatonin. This is a acid and coal tar ointment, applied be required to mask the taste commonly prescribed medication topically, for the treatment of characteristics of the APIs including used to treat insomnia and sleep psoriasis. The formulation for bitter, salty, acidic, and metallic disturbances in the paediatric and this preparation can be found in tasting drugs. A compounder can geriatric populations. Currently the numerous editions of the APF, prepare an oral liquid vehicle using only non-homeopathic melatonin including the latest. a proprietary base or may prepare product available on the market a base themselves. There are many is an oral prolonged release 2 mg Trichloroacetic acid paste, also proprietary bases on the market tablet (CircadinTM). known as Upton’s paste, is an APF including syrups, suspensions, formulation used for the treatment mixes (combination of and A number of these patients are of warts9 that is still compounded suspension), and some of which unable to swallow the commercial today. The formulation contains are pH buffered. product. Compounders are able trichloroacetic acid 10 g, salicylic to prepare an oral suspension acid 60g and glycerol 20 g. It is A commonly compounded oral of melatonin to overcome prepared by triturating together liquid suspension is omeprazole, the swallowing issue of these trichloroacetic acid and salicylic a proton pump inhibitor used populations, with 2 mg/mL being acid. Glycerol is then added until a in the treatment of Gastro- the most commonly prepared stiff paste is formed.9 oesophageal reflux disease. strength.26 Currently in Australia, there are Oral liquids commercially available tablets and Xerostomia, also known as dry Oral liquids are prepared for capsules. However, the majority of mouth, is a condition where

7 Compounding Table 2: Relationship between the drug release, drug and base in , low partitioning out of the . 12 base, and consequently an under- dose for the patient.13 Drug:base characteristics Approximate drug-release rate Troches Troches are sub-buccal absorbed Oil-soluble drug: oily base Slow release; poor escaping lozenges, formulated to dissolve tendency slowly in the buccal cavity, used Water-soluble drug: oily base Rapid release for both local and systemic effects. They can also be formulated to be chewed and swallowed which has Oil-soluble drug: water-miscible Moderate release rate benefits for paediatric and geriatric base patients.5 When used for systemic Water-miscible drug: water- Moderate release; based on effects the preparation is able to miscible base diffusion; all water soluble be dosed sub-buccally, avoiding first-pass metabolism, potentially allowing a reduction in the dose of patients suffer from reduced the API characteristics with those the API. salivary flow causing a dry mouth.27 of the base and the intended drug Pilocarpine is a treatment used release rate. An example of when a to increase salivary flow.28 This is compounder may compound a used as an oral rinse by patients Diazepam 10 mg suppositories, troche is when a patient presents who suffer from xerostomia, compounded for use during to the pharmacy with symptoms compounded by pharmacists, as epileptic seizures, need to be of burning mouth syndrome. The currently there is no appropriate prepared in a water-soluble base patient has tried several topical commercial product. such as polyethylene glycol, in and oral treatment options, order to facilitate rapid release of which resulted in significant side Suppositories the active from the base. The rapid effects. After consultation with Suppositories are solid dosage release is a result of the aqueous the patient and the physician, it forms used for rectal and vaginal base dissolving in the aqueous may be determined to compound administration of APIs for both mucosal of the rectum or a Clonazepam troche formulation local and systemic delivery. They vagina resulting in greater contact for local effect, which has been may be prepared with a variety of the API with the membrane shown to be safe and effective of bases including oil-soluble and wall, making it available for in the treatment of burning water-soluble bases. absorption.13 The ramifications mouth syndrome.18, 19 A gelatine- of choosing an inappropriate base troche preparation slowly Dyspareunia (pain on sexual base was demonstrated in a case dissolves in the mouth for local activity) is a condition women in USA when a teenager was therapy, reducing the systemic side suffer from associated with a treated with 10 mg compounded effects.19 variety of causes, from structural diazepam suppositories, yet to physiological, including vaginal presented to hospital on a number Oral progesterone is associated atrophy. When DHEA of occasions with uncontrollable with a large number of adverse are prescribed for such patients, seizures, despite the correct use events.33 In particular drowsiness, they need be compounded 29, as of the diazepam suppositories. which can be caused by the potent currently there are no commercial The lipophilic diazepam was positive allosteric modulators DHEA pessaries available on the compounded in cocoa butter, of GABAA receptors, due to the Australian market. which is a fatty acid base. The use progesterone metabolites, for When choosing which base of an oil-soluble drug in an oily example allopregnanolone.34 to compound with there is an base resulted in the API affinity A sub-buccal troche may be extreme importance in examining for the base rather than the rectal compounded, which will aim to 8 Compounding reduce the adverse effects by Canberra: Pharmaceutical reducing first pass metabolism, References Society of Australia, 2018 thereby allowing a reduction in the 1. Guidelines on compounding 10. Bussin E, Cairns B, Bovard dose administered and potentially of medicines [Internet]. The J, Scott A. Randomised reducing adverse events. Pharmacy Board of Australia; controlled trial evaluating the 2017 [cited 27 June 2018]. short-term analgesic effect of Conclusion Available from: http://www. topical diclofenac on chronic To ensure quality use of medicines, pharmacyboard.gov.au/Codes- Achilles tendon pain: a pilot compounding pharmacists are Guidelines.aspx study. BMJ Open. 2017; 7(4): compelled to use multiple levels of 2. Marriott J, Wilson K, Langley e015126. consciousness when determining C, Belcher D. Pharmaceutical 11. Bassani A, Banov D, Phan whether and how to compound compounding and H. Characterization of the a preparation for their patients. dispensing. 2nd ed. London: Percutaneous Absorption of Compounding is far more than Pharmaceutical Press; 2010. Ketoprofen Using the Franz just the manual dexterity of 3. Learn About Pharmacy Skin Finite Dose Model. preparing the dosage form. The Compounding at MEDISCA Postgraduate Medicine. most appropriate dosage form [Internet]. MEDISCA. 2018 2016; 128(2):262-267. for the specific patient needs [cited 3 July 2018]. Available 12. Allen L. The Basics of to be chosen, delivered by an from: https://www.medisca. Compounding. Compounding appropriate delivery vehicle for com/compounding Suppositories: Part One – the specific API required. The 4. [Internet]. Pharmacycouncil. Theoretical Considerations. compounding is to be conducted nsw.gov.au. 2018 [cited 3 July International Journal by appropriately trained staff, 2018]. Available from: https:// of Pharmaceutical following SOPs in appropriate www.pharmacycouncil.nsw. Compounding. 2000; facilities, using appropriate gov.au/sites/default/files/fact_ 4(4):289-293. equipment and the highest quality sheet_raw_materials_used_in_ 13. Allen L. BASICS OF ingredients on the market. Risk compounding_may_2018.pdf COMPOUNDING: Clinical management includes making the 5. Allen L. Art, Science, and Pharmaceutics, Part 2. decision not to compound if the Technology of Pharmaceutical International Journal identified and assessed risks in Compounding, (The) 5e. of Pharmaceutical the given compounding conditions Washington, DC: American Compounding. 2016; cannot be adequately mitigated. Pharmacists Association; 2016. 20(6):485-493. 6. Remington: The Science and 14. Allen L. The Basics of Compounding today allows Practice of Pharmacy. London: Compounding: Compounding the preparation of customised Pharmaceutical Press; 2012. Gels. International pharmaceutical treatment options 7. The Pharmaceutics and Journal of Pharmaceutical for patients. Compounding Compounding Laboratory Compounding. 1999; pharmacists are able to change the [Internet]. Pharmlabs.unc. 3(5):385-389. route of delivery of medications, edu. 2018 [cited 3 July 2018]. 15. Trissel L. Trissel’s stability of change the dosage form for the Available from: https:// compounded formulations. same route of delivery, remove pharmlabs.unc.edu/labs/ Washington, DC: APhA; 2012. allergens, and prepare medications capsules/punch.htm 16. Allen L. The Basics that are not commercially 8. THE SCIENCE OF of Compounding - available. This flexibility increases PHARMACEUTICAL Compounding Ointments the treatment options available COMPOUNDING: NON-STERILE and Pastes. International to clinicians in the treatment of TRAINING. Montreal: LP3 Journal of Pharmaceutical patients, with the underlying aim Network Inc.; 2018. Compounding. 1999; 3(1):22- being to improve therapeutic 9. Sansom LN, ed. Australian 24. outcomes. pharmaceutical formulary 17. Nagel K, Ali F, al-Khudari S, and handbook. 24th edition. Khan A, Patel K, Patel N et al. 9 Compounding Extemporaneous Compounding Dermatology. 2015;173(1):300- Biopharmaceutics Classification of Medicated Ointments. 302. System (BCS) of the Drugs. International Journal of 25. Sartor L, Trepanier L, Kroll M, International Journal of Pharmaceutical Compounding. Rodan I, Challoner L. Efficacy Pharmaceutical Compounding. 2010; 14(6):472-478. and Safety of Transdermal 2013;17(5):424-431. 18. Burning mouth syndrome Methimazole in the Treatment 32. Aceves S, Bastian J, - Diagnosis and treatment of Cats with Hyperthyroidism. Newbury R, Dohil R. Oral - Mayo Clinic [Internet]. Journal of Veterinary Internal Viscous Budesonide: A Mayoclinic.org. 2018 [cited Medicine. 2004;18(5):651. Potential New Therapy for 3 July 2018]. Available from: 26. Friciu M, Savji T, Zaraa S, Leclair Eosinophilic Esophagitis https://www.mayoclinic.org/ G. Evaluation of stability of in Children. The American diseases-conditions/burning- melatonin in extemporaneously Journal of Gastroenterology. mouth-syndrome/diagnosis- compounded oral suspensions. 2007;102(10):2271-2279. treatment/drc-20350917 Journal of Pharmacy Practice 33. FUNCTIONAL AND 19. 5. Zur E. Burning Mouth and Research. 2016;46(1):28- PERSONALISED HORMONE Syndrome - A Discussion 33. RESTORATION THERAPY of Complex Pathology. 27. Frydrych A. Dry mouth: Montreal: LP3 Network Inc.; International Journal of Xerostomia and salivary gland 2018. Pharmaceutical Compounding. hypofunction. Australian Family 34. Söderpalm A, et al. 2012; 16(3):196-205. Physician. 2016;45(7):488-492. Administration of progesterone 20. Editorial: The NPS 28. Kim J, Ahn H, Choi J, Jung produces mild sedative-like MedicineWise vision for D, Kwon J. Effect of 0.1% effects in men and women. Australian Prescriber. pilocarpine on Psychoneuroendocrinology. Australian Prescriber. 2016Jan; xerostomia: double-blind, 2004;29(3):339-54. 39(3). randomised controlled trial. 35. GOLDBERG D. Aspirin: Turn- 21. Soni A, Gowthamarajan K, Journal of Oral Rehabilitation. of-the-Century Miracle Drug. Radhakrishnan A. Personalized 2013;41(3):226-235. Distillations. 2009;. Medicine and Customized 29. Labrie F, Archer D, Bouchard 36. Mahdi J. Medicinal potential of Systems: The C, Fortier M, Cusan L, willow: A chemical perspective New Trend of Drug Delivery Gomez J et al. Intravaginal of aspirin discovery. Journal and Disease Management. dehydroepiandrosterone of Saudi Chemical Society. International Journal of (prasterone), a highly efficient 2010;14(3):317-322. Pharmaceutical Compounding. treatment of dyspareunia. 37. Pirmohamed M. 2018;22(2):108-121. Climacteric. 2011;14(2):282- Pharmacogenetics and 22. Lee V. Personalized 288. pharmacogenomics. medicine: transforming drug 30. Khodaeiani E, Fouladi R, British Journal of Clinical development and healthcare. Amirnia M, Saeidi M, Karimi Pharmacology. 2001;52:345- Therapeutic Delivery. 2010; E. Topical 4% nicotinamide vs. 347. 1(5):615-619. 1% clindamycin in moderate 38. Professional Practice Standards 23. Mamas L, Mamas E. inflammatory acne vulgaris. Version 5, June 2017. Premature ovarian failure International Journal of Pharmaceutical Society of and dehydroepiandrosterone. Dermatology. 2013;52(8):999- Australia, 2017 Fertility and Sterility. 2009; 1004. 39. ESSENTIAL ELEMENTS OF 91(2):644-646. 31. Pinherrio V, Danopoulos P, PERSONALIZED ANALGESIC 24. Hiom S, Patel G, Newcombe Demirdjian L, Nogueira R, MEDICATIONS Montreal: LP3 R, Khot S, Martin C. Severe Dubois F. In vitro Evaluation Network Inc.; 2018. postherpetic neuralgia and of Extemporaneously 40. Walsh W. Nutrient power. other neuropathic pain Compounded Immediate- 2nd ed. New York: Skyhorse syndromes alleviated by topical release Capsules with Pre- Publishing; 2014. gabapentin. British Journal of mixed Excipients Based on the 10 Compounding CPD Multiple Choice Questions

1. Which of the following circumstances is compounding suitable?

A. The commercial product comes in a 2mg capsule whereas the patient’s dose is 4mg B. The patient is unable to afford the commercial product C. The patient has an allergy to the colour in the commercial product. D. The commercial product was removed from the market for safety concerns

2. The aims of compounding a medication for a patient include:

A. Improving patient compliance by reducing side effects B. Eliminating risk of allergy C. Improving therapeutic outcomes for patients D. Increasing therapeutic treatment options E. All of the above

3. Which of the following controls support the quality of compounded preparations?

A. Sourcing raw ingredients from TGA-approved manufacturers B. Implementing Standard Operating Procedures C. Following formulas which are published in reputable sources D. All staff involved undergoing competency-assessed training E. All of the above

4. All medications supplied to patients, both compounded and commercially available, are required to meet standards of efficacy, safety, and stability.

A. True B. False

5. Which of the following statements regarding compounding is INCORRERCT?

A. Simple compounding uses formulations for which information confirming quality, stability, safety, efficacy and rationality is available. B. Complex compounding is the preparation and supply of a single ‘unit of issue’ of a therapeutic product that is intended for supply for a specific patient, that requires or involves special competencies, equipment, processes or facilities C. All APF formulations are classed as simple compounding D. Sterile preparations are examples of complex compounding E. Preparations containing ingredients posing an occupational health and safety hazard are classed as complex compounding.

11 Compounding

6. Which of the following statements regarding capsules is CORRECT?

A. All capsule shells are composed of Gelatine B. The smaller the capsule size number, the smaller the volume it contains. C. Commonly used capsule fillers include microcrystalline cellulose, lactose, hypromellose, and mannitol D. A compounder may compound a capsule when a commercial product has been removed from the market for safety reasons E. ALL of the above

7. Which of the following statements regarding compounded oral liquids is INCORRECT?

A. Oral liquids are prepared for patients who have difficulty swallowing solid dosage forms. B. Compounders should only prepare an oral liquid vehicle bases themselves. C. Oral liquid preparations include aromatic waters, linctuses, mixtures, suspensions, and syrups. D. Oral liquids are susceptible to chemical, physical, and microbial instability. E. Various flavours and sweeteners may be required to mask the taste of some APIs.

8. Which of the following statements regarding compounding suppositories is CORRET?

A. An oil-soluble drug compounded into an oily base will produce a suppository with a moderate release rate. B. An oil-soluble drug compounded into a water-miscible base will produce a suppository with a slow release rate. C. A water-miscible drug compounded into a water-miscible base will produce a suppository of extremely slow release. D. A water-soluble drug compounded into an oily base will produce a suppository with a rapid release rate. E. ALL of the above.

Accreditation Number: A1809AJP5 Expiry: 01/09/2020 This activity has been accredited for 1.5 hour of Group 1 CPD (or 1.5 CPD credits) suitable for inclusion in an individual pharmacist’s CPD plan which can be converted to 1.5 hour of Group 2 CPD (or 3.0 CPD credits) upon successful completion of relevant assessment activities.

First published in the Australian Journal of Pharmacy online version. 1st September 2018. Reproduced and distributed by the Medisca Group of companies with the permission of the publisher.

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