Summary PTB2

Summary PTB2

Lecture 1 Introduction (Woerdenbach)

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
API and dosage form determine the biopharmaceutical properties
Biopharmaceutical properties are leading for the (design of) the dosage form and the route
of administration.

Excipients like a emulsifier, vehicle, antioxidant, 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

Types of action:
Systemic: API reaches its site of action via the blood stream
Local: API is administered at the site where it should be

Legal status of medicines:
Pharmaceutical preparations (branded products)
 Commercially available
 Industrially manufactured
 Licensed
o Marketing authorization granted from competent authorities, based on
safety, quality, efficacy
o Registration dossier
 Independent supervision
o Government, national inspection

Extemporaneous pharmacy preparations are prepared on demand (prescription) in the
pharmacy (Hospital, community pharmacy). It is tailor-made for the patient (personalized
medicine). It is an unlicensed preparation
 Independent supervision lacks: Additional responsibilities required from professional
health care workers like pharmacist to assure quality (prescribing, preparation)(so no
strict quality control and regulatory oversight)

Dutch Medicines Act (Geneesmiddelenwet): Pharmacists allowed to prepare a drug product
for patients in own pharmacy
Dutch Health and Youth Care Inspectorate (Inspectie voor Gezondheidszorg en Jeugd IGJ)
makes the frame work for pharmacy preparations
Royal Dutch Pharmacists Association KNMP: makes guidelines for pharmacy preparations,
emphasizing pharmacotherapeutically rationality(good design), and adherence to Dutch
Pharmacist’s Formulary FNA: standardized procedures and formulations; This formulary

,serves as a valuable resource for pharmacists in the Netherlands, offering guidance on
compounding medications in accordance with established standards.

Pharmacy preparations: The ‘manufacture’ of unlicensed pharmaceutical preparations by or
at the request of pharmacies or other healthcare establishments. The (Dutch) pharmacist is
legally allowed to prepare and dispense pharmaceutical dosage forms in response to a
health practitioner’s prescription
Pharmacy preparations(personalized medicine) used because
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)

When pharmacy preparations?
 Dose adjustment
 Dosage form adjustment (other route of administration rectal i.p.v oral)
 Hypersensitivity to excipients
 Unavailability of a product on the market
 Modification of industrial preparation
 Short shelf life: making it impractical to stock large quantities. pharmacists prepare
smaller quantities, reducing waste.
 Investigational medicinal product (product in clinical trial, not yet on market)

Types of pharmacy preparations
Compounded from raw materials like the drug substance(s) and excipients
Modification or manipulation of commercially available licensed dosage forms to suit
specific patient requirements. This involves altering an existing pharmaceutical product, such
as pulverizing tablets to create a capsule or conversion of oral solid dosage form into oral
liquid dosage form. There is a risk of encountering pharmaceutical technological and
biopharmaceutical problems when manipulating dosage forms, potentially affecting the
stability and efficacy of the medication.
Preparation prior to use: Dutch: VTGM = voor toediening gereedmaken
These preparations involve handling or preparing a medication shortly before
administration. E.g. Reconstitution of injection fluid, Filling medication pump with injection
from ampoule, Dissolving freeze-dried antibiotic in water to create oral solution

Quality assurance final product:
Europian Pharmacoupia: Essential requirements for most common dosage forms - No
monographs (yet) for individual preparation
GMP Good Manufacturing Practice is a set of quality assurance principles and guidelines
ensuring that pharmaceutical products are consistently produced and controlled to the
quality standards appropriate for their intended use. GMP is primarily designed for large-
scale, industrial pharmaceutical manufacturing facilities.

,It aims to provide a systematic framework for the production of pharmaceuticals under
controlled and consistent conditions, To guarantee good product quality
Pharmacists often interpret industrial GMP guidelines to fit the context of pharmacy
preparations, developing adapted guidelines that prioritize factors relevant to their practice.
The goal is to assure manufacture or production under controlled conditions, even if those
conditions may differ from large-scale industrial settings.

Standardised formulations refer to predetermined recipes or formulas for preparing specific
medications. These formulations are established by regulatory bodies like the KNMP.

From prescription to dispensing
Before prescribing or dispensing a medication, there should be a solid pharmacotherapeutic
rationale: comprehensive assessment of the patient's medical condition, history, and any
other relevant factors to determine the most appropriate
treatment.
1st choice: commercially available preparation
2nd choice: pharmacy preparation
 standardised(protocols)
 Non-standardised (noprotocols)
Risk assessment, we look at the benefit for patient and
possible risk related to quality level.
Responsibility for prescriber and pharmacist: Pharmacist
is co-responsible for patient treatment

Standardization ->Applicable for routinely made pharmacy preparations
The composition and preparation method are designed in advance and validated. This means
that before the actual production, a specific formula or protocol is established: Each batch is
prepared according to the corresponding procedure(s) and formula(protocol and has the
desired (high) quality
Standardization involves defining and maintaining consistency in several aspects:
Batch size, Composition, Preparation method and Materials and equipment used
In-process controls and end controls are implemented during the preparation process to
ensure quality at various stages.
Any deviations from the established procedure should be validated->so must be
justified/confirmed to ensure quality of product.

Standardized preparations:
The FNA is likely a reference or guideline used by pharmacists in the Netherlands. It could
contain standardized information and procedures related to pharmacy preparations.
 Formulations: oral, dermal, rectal etc.
 Preparation methods
 Storage, packaging, leaflet
 Background information (effectiveness, safety, stability)

Non-standardized preparations
 No formulation readily available
 Single patient (or only few patients)

,  Before preparation ->The pharmacist takes responsibility for designing and preparing
the medication: Evaluation of effectiveness, safety and quality. Risk assessment: less
well-documented quality versus patient benefit
 Design and production process drafted from scratch: Minimum set of quality
requirements like composition, stability, biopharmaceutical performance. Pharmacist
stick to general procedures as much as possible. Consider practical applicability, ease
of use, safety for patient and compounder

Product file:
 Compiled in advance
 Supports the preparation
 Limited or comprehensive
In product file is noted: Pharmacotherapy, Specifications of drug substance and excipients,
Design of the formulation and preparation, Equipment (incl. standard operating procedures
(SOPs)->each compound has its own procedure), Trial preparation(first preparation), Test
results, Criteria for release, Stability, Storage conditions, Package, labelling, patient
information

Preparation record: (Batch) preparation record (master file, supported by a product file) →
preparation instruction (for each single batch). Contains all information relevant for the
pharmacy preparation and the manufacture process. Like the Batch size, Formulation and
method of preparation and Storage conditions and shelf-life, Package, labelling
Release is based on completed preparation instruction: Data recorded during and after
preparation
Document for accountability: archived

In process controls IPC is the result of a handling, not a handling itself->identify critical steps
in a preparation. Monitor and guard these steps. Built-in quality (= GMP!)

Summary:
Drug compounding provides added value to clinical care: Pharmacotherapeutic rationale,
Standardization of procedures and formulations, Production and control according to quality
standards and explicit role for the pharmacist
Pharmacy preparations will remain important in view of the increasing interest in
personalized medicine: Flexibility, tailor-made approach. Improved pharmacotherapeutic
outcome

Lecture 2 Basic operations (Woerdenbach)
Weighing: Determination of the mass of an object or of a quantity of a substance
Choose the right balance (right weighing range), use it carefully and maintain it in good
order. Submit to periodical metrological control->to verify its accuracy. Clean, levelled, calibrated

Use clean spatula or spoon, Weigh on paper sheet (solid), on greaseproof paper or cellophane
(semisolid), in vessel or container (liquid)

Weighing is more accurate and precise than volume measurement
 Liquids are often weighed (especially viscous ones)