Summary Pharmaceutical Technology and Biopharmacy
(Woerdenbag)
Pharmacy preparations
Product care
- To ensure availability of the proper medicine, in the right dosage form, of good quality for the
patient at the time of administration
- Purchasing - stock management - storage - compounding (if applicable) - dispensing - patient
counseling
- Pharmaceutical care
- Pharmaceutical patient care
- Product care
What is a medicine?
- A pharmacologically active substance (drug substance, active pharmaceutical ingredient (API))
manufactured into a suitable dosage form (drug product)
- Dosage form consists of active compound(s) plus excipients (hulpstoffen)
- API and dosage form determine the biopharmaceutical properties
- Biopharmaceutics is leading for the (design of) the dosage form and the route of administration
Excipients
- Excipients are part of each formulation, in order to
- Facilitate production
- Improve quality of the product
- Optimize performance of the product
- Increase patient acceptability and compliance
Diluent, Filler, Vehicle, Emulsifier, Viscosity enhancer, Preservative, Antioxidant, Flavour, Colour,
pH correctant, Stabilizer
A medicine, made for the patient
COMPOSITION process
API + STRUCTURE
excipients
functionality
A medicine, made for the patient
PRODUCT
use
Types of action
- Systemic
- API reaches its site of action via the blood stream PATIENT
- Local
- API is administered at the site where it should act
ADMI (Absorption, Distribution, Metabolism, Elimination)
Biopharmaceutics
Pagina 1 van 87
,Systemic and local action
Administration route Dosage form
Oral Tablet, powder, capsule, granules (solid); solution, suspension,
emulsion, gel (liquid)
Rectal Suppository, enema
Vaginal Pessary
Parenteral Injection (solution, suspension, emulsion)
Dermal Ointment, cream, paste, lotion, gel, solution, dusting powder,
transdermal patch
Pulmonary Aerosol (solution, suspension, emulsion, powder), inhalation, spray,
gas
Nasal Drop, spray, (solution, suspension)
Auricular Drop (solution, suspension), ointment, cream
Ocular Drop (solution, suspension), ointment, cream
Legal status of medicines
Pharmaceutical preparations (branded products)
- Commercially available
- Industrially manufactured
- Manufacturing authorization granted from competent authors
- Licensed
- Marketing authorization granted from competent authorities, based on safety, quality, efficacy
- Registration dossier
- Independent supervision
- Government, national inspection
Legal status of medicines
Extemporaneous pharmacy preparations (prepared in pharmacies)
- Prepared on demand (for one single patient)
- Hospital pharmacy, community pharmacy
- Tailor-made for the patient (personalized medicine)
- Unlicensed
- Independent supervision lacks
- Additional responsibilities required from professional health care workers to assure quality
(prescribing, preparation)
The Netherlands
- Dutch Medicines Act
- Geneesmiddelenwet (July 2007)
- Pharmacist is allowed to prepare a drug product for patients in own pharmacy
- Dutch Health and Youth Care Inspectorate
- Inspectie voor de Gezondheidszorg en Jeugd (IGJ).
- Framework for pharmacy preparations
- Royal Dutch Pharmacists Association (KNMP)
- Guidelines for pharmacy preparations
- Pharmacotherapeutically rational, good design
- Dutch Pharmacist’s Formulary
- FNA: Formularium der Nederlandse Apothekers
- Standardized formulations, general procedures
Pagina 2 van 87
,Pharmacy preparations
- European Pharmacopoeia definition: The ‘manufacture’ of unlicensed pharmaceutical
preparation by or at the request of pharmacies to other healthcare establishments
- The (Dutch) pharmacist is legally allowed to prepare and dispense pharmaceutical dosage forms
in response to a health practitioner’s prescription
- Competent by education, training and practice
Why pharmacy preparations?
- To optimize pharmacotherapy for a patient
- Commercial products insufficiently meet specific requirements
- Commercial products are unavailable
- Tailor-made approach
- To increase patient compliance
- More flexibility
- Better acceptance by the patient (convenience)
Personalized medicine!
When pharmacy preparation?
- Dose adjustment
- Dosage form adjustment (other route of administration)
- Hypersensitivity to excipients
- Unavailability of a product on the market
- Modification of industrial preparation
- Short shelf-life (immediately given to the patient)
- Investigational medicinal product
Case
- Anne, 8 years, uses sodium valproate oral solution (Depakine) as prophylactic against epilepsy.
She now suffers from nausea and vomiting. The physician asks the pharmacist to replace oral
sodium valproate by an appropriate rectal dosage form for a period of 4 days
- The pharmacist prepares and dispenses Valproic acid suppositories 250 mg (standardized
preparation, according to the Dutch Pharmacist’s Formulary), after he has controlled the dose.
Types of pharmacy preparations
- Compound from raw materials
- Drug substance(s) + excipients
- Manipulated (commercially available) licensed dosage forms
- Risk of pharmaceutical technological and biopharmaceutical problems
- Pulverizing tablets to make capsules
- Conversion of oral solid dosage form into oral liquid dosage form
- Preparation prior to use
- Product designed to undergo such handling
- Reconstitution of injection fluid (dissolve powder and fill sirange)
- Filling medication pump with injection from ampoule
- Dissolving freeze-dried antibiotic in water to create oral solution
- Dutch: VTGM = voor toedoening gereedmaken
Compounding: examples
Suppository, Mixing, Capsules filled, Medication cassette
Pagina 3 van 87
, Quality assurance final product
- European Pharmacopoeia (Ph. Eur.)
- Monograph Pharmaceutical Preparations
- Essential requirements for most common dosage forms
- No monographs (yet) for individual preparations
- United States Pharmacopoeia/National Formulary (USP-NF)
- Chapter Pharmacy Compounding - Sterile Preparations
- Chapter Pharmacy Compounding - Non-sterile Preparations
- Chapter Quality Assurance in Pharmaceutical Compounding
- Monographs for Compounded Preparations
- Built-in quality (GMP)!
Quality assurance in production
- Industrial production
- Good Manufacturing Practice (GMP)
- Pharmacy preparations
- GMP guidelines interpreted to fit in the context in which the manufacture takes place
- Several aspects of GMP are also applicable for non-industrial pharmacy preparation but full
industrial GMP is unfeasible
- Developments of adapted guidelines
- To assure manufacture of production under controlled conditions
- To guarantee good product quality
Standardized formulation
- Royal Dutch Pharmacists Association
- Standardized procedures
- Standardized formulations
- Smaller scale pharmacy preparations
- Scientifically based
- In close cooperation with the field
From prescription to dispensing
- Solid pharmacotherapeutic rationale
- First choice: commercially available preparation
- Second choice: pharmacy preparation
- Standardized (protocols)
- Non-standardized (no protocols)
- Risk assessment
- Benefit for patient
- Possible risk related to quality level
- Responsibility for prescriber and pharmacist 23
31-07-2018 | 23
- Pharmacist is co-responsible for patient treatment
Decision tree 2
3
Pharmacotherapeutic rationale
Commercial product available? Y Order
Dispense
N
Standardised formulation? Y Compound Dispense
Decision tree N
Evaluate technical and Evaluate Evaluate
biopharmaceutical aspects health risk environmental aspects
N
Risk assessment: Y
Compound Dispense
Pharmacy preparation has added value
N
Discuss alternative
Pagina 4 van 87
(Woerdenbag)
Pharmacy preparations
Product care
- To ensure availability of the proper medicine, in the right dosage form, of good quality for the
patient at the time of administration
- Purchasing - stock management - storage - compounding (if applicable) - dispensing - patient
counseling
- Pharmaceutical care
- Pharmaceutical patient care
- Product care
What is a medicine?
- A pharmacologically active substance (drug substance, active pharmaceutical ingredient (API))
manufactured into a suitable dosage form (drug product)
- Dosage form consists of active compound(s) plus excipients (hulpstoffen)
- API and dosage form determine the biopharmaceutical properties
- Biopharmaceutics is leading for the (design of) the dosage form and the route of administration
Excipients
- Excipients are part of each formulation, in order to
- Facilitate production
- Improve quality of the product
- Optimize performance of the product
- Increase patient acceptability and compliance
Diluent, Filler, Vehicle, Emulsifier, Viscosity enhancer, Preservative, Antioxidant, Flavour, Colour,
pH correctant, Stabilizer
A medicine, made for the patient
COMPOSITION process
API + STRUCTURE
excipients
functionality
A medicine, made for the patient
PRODUCT
use
Types of action
- Systemic
- API reaches its site of action via the blood stream PATIENT
- Local
- API is administered at the site where it should act
ADMI (Absorption, Distribution, Metabolism, Elimination)
Biopharmaceutics
Pagina 1 van 87
,Systemic and local action
Administration route Dosage form
Oral Tablet, powder, capsule, granules (solid); solution, suspension,
emulsion, gel (liquid)
Rectal Suppository, enema
Vaginal Pessary
Parenteral Injection (solution, suspension, emulsion)
Dermal Ointment, cream, paste, lotion, gel, solution, dusting powder,
transdermal patch
Pulmonary Aerosol (solution, suspension, emulsion, powder), inhalation, spray,
gas
Nasal Drop, spray, (solution, suspension)
Auricular Drop (solution, suspension), ointment, cream
Ocular Drop (solution, suspension), ointment, cream
Legal status of medicines
Pharmaceutical preparations (branded products)
- Commercially available
- Industrially manufactured
- Manufacturing authorization granted from competent authors
- Licensed
- Marketing authorization granted from competent authorities, based on safety, quality, efficacy
- Registration dossier
- Independent supervision
- Government, national inspection
Legal status of medicines
Extemporaneous pharmacy preparations (prepared in pharmacies)
- Prepared on demand (for one single patient)
- Hospital pharmacy, community pharmacy
- Tailor-made for the patient (personalized medicine)
- Unlicensed
- Independent supervision lacks
- Additional responsibilities required from professional health care workers to assure quality
(prescribing, preparation)
The Netherlands
- Dutch Medicines Act
- Geneesmiddelenwet (July 2007)
- Pharmacist is allowed to prepare a drug product for patients in own pharmacy
- Dutch Health and Youth Care Inspectorate
- Inspectie voor de Gezondheidszorg en Jeugd (IGJ).
- Framework for pharmacy preparations
- Royal Dutch Pharmacists Association (KNMP)
- Guidelines for pharmacy preparations
- Pharmacotherapeutically rational, good design
- Dutch Pharmacist’s Formulary
- FNA: Formularium der Nederlandse Apothekers
- Standardized formulations, general procedures
Pagina 2 van 87
,Pharmacy preparations
- European Pharmacopoeia definition: The ‘manufacture’ of unlicensed pharmaceutical
preparation by or at the request of pharmacies to other healthcare establishments
- The (Dutch) pharmacist is legally allowed to prepare and dispense pharmaceutical dosage forms
in response to a health practitioner’s prescription
- Competent by education, training and practice
Why pharmacy preparations?
- To optimize pharmacotherapy for a patient
- Commercial products insufficiently meet specific requirements
- Commercial products are unavailable
- Tailor-made approach
- To increase patient compliance
- More flexibility
- Better acceptance by the patient (convenience)
Personalized medicine!
When pharmacy preparation?
- Dose adjustment
- Dosage form adjustment (other route of administration)
- Hypersensitivity to excipients
- Unavailability of a product on the market
- Modification of industrial preparation
- Short shelf-life (immediately given to the patient)
- Investigational medicinal product
Case
- Anne, 8 years, uses sodium valproate oral solution (Depakine) as prophylactic against epilepsy.
She now suffers from nausea and vomiting. The physician asks the pharmacist to replace oral
sodium valproate by an appropriate rectal dosage form for a period of 4 days
- The pharmacist prepares and dispenses Valproic acid suppositories 250 mg (standardized
preparation, according to the Dutch Pharmacist’s Formulary), after he has controlled the dose.
Types of pharmacy preparations
- Compound from raw materials
- Drug substance(s) + excipients
- Manipulated (commercially available) licensed dosage forms
- Risk of pharmaceutical technological and biopharmaceutical problems
- Pulverizing tablets to make capsules
- Conversion of oral solid dosage form into oral liquid dosage form
- Preparation prior to use
- Product designed to undergo such handling
- Reconstitution of injection fluid (dissolve powder and fill sirange)
- Filling medication pump with injection from ampoule
- Dissolving freeze-dried antibiotic in water to create oral solution
- Dutch: VTGM = voor toedoening gereedmaken
Compounding: examples
Suppository, Mixing, Capsules filled, Medication cassette
Pagina 3 van 87
, Quality assurance final product
- European Pharmacopoeia (Ph. Eur.)
- Monograph Pharmaceutical Preparations
- Essential requirements for most common dosage forms
- No monographs (yet) for individual preparations
- United States Pharmacopoeia/National Formulary (USP-NF)
- Chapter Pharmacy Compounding - Sterile Preparations
- Chapter Pharmacy Compounding - Non-sterile Preparations
- Chapter Quality Assurance in Pharmaceutical Compounding
- Monographs for Compounded Preparations
- Built-in quality (GMP)!
Quality assurance in production
- Industrial production
- Good Manufacturing Practice (GMP)
- Pharmacy preparations
- GMP guidelines interpreted to fit in the context in which the manufacture takes place
- Several aspects of GMP are also applicable for non-industrial pharmacy preparation but full
industrial GMP is unfeasible
- Developments of adapted guidelines
- To assure manufacture of production under controlled conditions
- To guarantee good product quality
Standardized formulation
- Royal Dutch Pharmacists Association
- Standardized procedures
- Standardized formulations
- Smaller scale pharmacy preparations
- Scientifically based
- In close cooperation with the field
From prescription to dispensing
- Solid pharmacotherapeutic rationale
- First choice: commercially available preparation
- Second choice: pharmacy preparation
- Standardized (protocols)
- Non-standardized (no protocols)
- Risk assessment
- Benefit for patient
- Possible risk related to quality level
- Responsibility for prescriber and pharmacist 23
31-07-2018 | 23
- Pharmacist is co-responsible for patient treatment
Decision tree 2
3
Pharmacotherapeutic rationale
Commercial product available? Y Order
Dispense
N
Standardised formulation? Y Compound Dispense
Decision tree N
Evaluate technical and Evaluate Evaluate
biopharmaceutical aspects health risk environmental aspects
N
Risk assessment: Y
Compound Dispense
Pharmacy preparation has added value
N
Discuss alternative
Pagina 4 van 87
