Extemporaneous compounding

Question 1

What is extemporaneous compounding?

Answer 1

-manipulation of drugs and chemical ingredients via traditional compounding techniques to produce medications suitable for patients when no commercial forms are appropriate

Question 2

What is off label or unlicensed use?

Answer 2

• the use of medicines outside its product license or approval
• this can be for the treatment of a different disease or the use of medicine by different population groups

Question 3

What are the preferred dosage forms for infants 1month - 2 years old?

Answer 3

small volumes of liquids

e.g. syrups and solutions

Question 4

What are the preferred dosage forms for children (aged 2-5 years)?

Answer 4

• liquids

- effervescent tablets

Question 5

What are the preferred dosage forms for children 6-11 years ?

Answer 5

-solids like chewable tablets and orally disintegrating tablets

Question 6

What are the preferred dosage forms for adolescents (12-18 years)

Answer 6

-solids, typical adult dosage forms like tablets and capsules

Question 7

What are the reasons for compounding?

Answer 7

• required dosage form of a medicine does not exist/is not available
• allergy sensitivity to an inactive ingredient in manufactured products
• unavailability or discontinuation of a medicine
• requirement for different dose, concentration or route of administration
• novel therapies and specialist products used in hospitals and clinics

Question 8

Is compounding accurate?

Answer 8

-medicines manufactured by Pharma company will be more of a reliable quality than that compounded in pharmacies due to strict quality control processes and equipment, but sometimes compounding is necessary so we must learn the ground level principles and adapt to the situation.

Question 9

What are the risks assoc with extemporaneous compounding?

Answer 9

• formulation failure due to chemical and physical instability
• microbial contamination
• calculation errors
• patient acceptability issues
• health and safety risks
• therapeutic risks and clinical consequence

Question 10

What are some drugs not available as liquids?

Answer 10

• acetazolamide
• amlodipine
• captopril
• allopurinol
• lamotrigine
• omeprazole
• rifampin
• topiramate
• azathioprine
• levodopa/carbidopa
• amiodarone

Question 11

How is stability assessed?

Answer 11

• using various storage conditions
• chemical stability testing by HPLC
• physical stability testing for appearance, pH, viscosity, microbiology

Question 12

What storage conditions should compounded products be tested at?

Answer 12

• fridge: 4 degrees C
• room temperature: 20 degreesC
• 40 degrees C/75% RH

Question 13

What was the problem with ADHB phenobarbitone oral liquid ?

Answer 13

• contained phenobarbitone pure powder in a mixture of glycerol and water
• expired in 7 days if refrigerated
• had problems with stability, short date resulting in frequent compounding
• had an unacceptable taste leading to non compliance and treatment failure

Question 14

What was the result of the phenobarbitone investigation?

Answer 14

• recommended optimal flavour for SP base was lemon 0.75% w/v
• HOS formulation exp date extended to 6 weeks
• found to be liquid SP-F stable for 4 weeks (refrigeration optional)
• better palatability and visocsity properties

Question 15

What are the good sources of info to go for extemporaneous compounding?

Answer 15

• David Woods website
• Trissel’s stability of compounded formulations
• APF
• International journal of pharmaceutical compounding
• NZHPA CNO sig

Question 16

What are the steps to preparing paediatric oral liquids?

Answer 16

1. consider alternative drug
2. consider alternative method e.g. tablet dispersion or oral admin of injection
3. consult latest info databases and publications, prepare formulation according to published study and follow conditions as closely as possible. Modifications are only appropriate if there are no detrimental effects on stability

Question 17

What stability information and patient info is require in the preparation of paediatric oral liquids?

Answer 17

• may be possible to adapt existing info from drug stability texts e.g. solubility, pH stability profile, or from the formulation details of the injection or oral liquid available elsewhere
• provide info to carers to ensure correct use including storage conditions, use of oral syringe, shaking before admin.

Question 18

What are the suspending agents for oral liquid formulation?

Answer 18

• these are preformulated and flavoured suspending agents for insoluble drugs
• they can be used for bitter tasting drugs due to sweetening effect
• in NZ we have Ora-Blend, Oral Plus and Ora-sweet

Question 19

What are the neonatal adverse reactions for oral or parenteral benzyl alcohol?

Answer 19

-neurotoxicity, metabolic acidosis

Question 20

What are the neonatal adverse reactions for oral or parenteral ethanol?

Answer 20

-neurotoxicity

Question 21

What are the neonatal ADRs for parenteral polyethylene glycol?

Answer 21

metabolic acidosis

Question 22

What are the neonatal ADRs for parenteral Polysorbate 20 and polysorbate 80?

Answer 22

liver and kidney failure

Question 23

What are the neonatal ADRs for oral and parenteral propylene glycol?

Answer 23

seizures, neurotoxicity, hypoeromolarity

Question 24

What does Trissel’s stability of compounded formulations contain?

Answer 24

• properties (solubility, pH, pKa)
• general stability considerations
• stability reports of compounded products
• commercial availability

Question 25

What are the NZ standards and guidelines regarding extemporaneous compounding?

Answer 25

-under MA 26: pharmacists may sell, supply compounded medicines without a manufacturing license if a request is made by the person to whom the medicine is to be sold or supplied - no GMP obligation - requirement to meet professional standards - requirement to comply with pharmacy services standard

Question 26

What are the professional standards that extemporaneous compounding must meet?

Answer 26

-competence standard 7: preparation of pharmacuetical products in community and hospital pharmacies

Question 27

What is the pharmacy services standard 2010 that extemporaneous compounding must comply to?

Answer 27

-section 5: dispensing, compounding, repackaging and batch preparation

Question 28

What is the importance of the pharmacy services standard 2010?

Answer 28

- foundation for describing good practice and promoting continuous quality improvement - aims to ensure consumers receive safe and appropriate services - applicable to preparation of a medicine for an individual person in sufficient quantity to fulfil an individual prescription - also applies to small scale batch preparation in quantities that do not exceed those specified.

Question 29

What are the NZ compounding standards?

Answer 29

- quality management - good compounding, repackaging and batch preparation practice - SOPs - internal audit for QC - documentation for QC - procedures for QC - materials and product release - staffing requirements - training - personal hygiene