Formulation dermatological

Dermatological prescription means prescription, production and marketing of topical preparations which are produced under the responsibility of a pharmacist (as a rule in each case on demand) in a public pharmacy or hospital pharmacy. The individual prescription is based on the special circumstances of individual patients. In a narrower sense, the prescription is also referred to as the prescription formula and the prescription drug. Dermatological extemporaneous preparations are frequently referred to if prescriptions have proved their worth by experience or if rationally justifiable recommendations in relevant publications, in particular collections of corresponding recommendations are referred to. In connection with the standardization of prescription bases and prescriptions, the current pharmacopoeia is of special importance in Germany, possibly also earlier editions including the (former) pharmacopoeia of the GDR as well as the DAC and the "Neues Rezeptur-Formularium" ( NRF). As far as such specifications are not used, these are individual prescriptions.

As far as pharmaceutical quality and benefit/risk assessment are concerned, physicians and pharmacists fulfill their responsibility towards patients in dermatological extemporaneous preparations in a special way by following current principles as far as possible and implementing them in professional practice. The benefit consists in the treatment of diseases of the skin organ with the aim of their elimination; the risk may consist in local or systemically mediated adverse drug reactions in the treated patient and/or exposure of the human environment.

Quality management is of essential importance in dermatological prescriptions. Individual physicians and pharmacists bear responsibility for this, as do chambers, professional societies, professional associations and drug manufacturers who provide components. The quality of the dermatological formulation is to be considered under the aspects of structure, process and result quality in each case individually as well as overall. Measures of internal as well as external quality control (interlaboratory tests) are to be aimed at.

To avoid delays and errors, dermatological prescriptions should be issued precisely and unambiguously. Salts or solvates or derivatives of ingredients must be named correctly to avoid incorrect dosing or inefficacy. In the case of identifiable errors, the pharmacist must resolve the ambiguity by consulting with the physician prior to preparation. Even in the event that the actual intention of the prescriber becomes sufficiently apparent, at least subsequent information should be provided to avoid repetition. Consultations are also regularly required prior to the preparation of such extemporaneous preparations which contain controversial medicinal substances, which contain ingredients whose quality can only be assured to a limited extent, whose exact method of application is unclear, which cannot be expected to have any or only insufficient efficacy due to interactions of the ingredients, or whose pharmaceutical quality would be insufficient for various reasons without a change in the formulation.

The restriction to one or a few drug concentrations in finished drug externals is a major motive for prescribing extemporaneous preparations with individually deviating concentrations. In this respect, deviations from the standard concentration may be intentional or due to an error. Since medicinal substances which are inadvertently too highly concentrated may considerably endanger the patient, selected dermatics active agents with so-called upper therapeutic guideline concentrations are listed in the NRF (Tab. I.6.-1) at the suggestion of the Commission for Extemporaneous Prescriptions of the DDG. If these concentrations are exceeded in prescriptions, the physician is to indicate his intention by means of an exclamation mark. In the absence of such a notation, the pharmacy must clear up the ambiguity prior to preparation.

The quality of the prescription ingredients required by pharmaceutical law must be determined and documented by the pharmacist. In principle, therefore, only basic substances and preparations provided with a test certificate in accordance with §§ 6 and 11 ApBetrO or with complete quality documentation specific to the pharmacy, marketable finished medicinal products or substances and preparations manufactured in the pharmacy in accordance with recognized pharmaceutical rules may be prescribed, processed and placed on the market in prescriptions.

When assessing the safety of medicinal products, physicians and pharmacists must take into account the current state of knowledge of the medical and pharmaceutical sciences, as it can be found, among other things, in statements by the BfArM or the AMK and the AKdÄ as well as in scientific articles in professional journals. The monographs officially published in the context of the reauthorization of finished medicinal products by processing scientific knowledge material are to be observed in the assessment. In case of doubt, information should be obtained, for example, from institutions of the chambers, from professional societies, professional associations or from the competent authorities.

Prescriptions of concern must not be prescribed, manufactured or dispensed. Among other things, the concern may arise directly from the pharmacological-toxicological properties of certain drug substances or other formulation components or from the interaction of components or against the background of the intended dose, concentration, method of application and duration of use.

A benefit-risk assessment of pharmacologically/toxicologically controversial ingredients or formulations is to be carried out against the background of therapeutic alternatives. In the case of negative monographs or otherwise predominantly negatively assessed ingredients (or formulations), the benefit/risk assessment must be carried out in each individual case. In particular, an exceptionally positive assessment should be documented in writing, for example using the template according to NRF, Figure I.5.-1. Economic considerations must not play a role in this context.

Extemporaneous preparations should be composed under rationally comprehensible aspects and contain medicinal substances in therapeutically effective concentrations in each case. Two or more medicinally active ingredients should be combined in externals only in justified exceptional cases.

Multiple combinations are not only increasingly difficult to rationally comprehend as the number of medicinal substances increases, but their pharmaceutical quality can hardly be monitored and assured. This applies in particular to the processing of finished drugs in a formulation.

If possible, the identical base, or at least a base of the same type, should be used to dilute a finished drug.

Extemporaneous preparations must be packaged in such a way that the required drug quality is guaranteed in the intended period of use and the drug can be used as intended and safely. Packaging recommendations of the AMK, the NRF and the ZL should be observed. When available, primary packaging materials certified to contemporary specific standards should be used, for example, in accordance with Appendix H of the DAC or ZL packaging regulations.

Dermatologic extemporaneous preparations must be prepared in a hygienic manner and remain so during the period of use. In certain cases this means sterility, as a rule a germ count limitation to no more than 100 germs per gram or milliliter with the exclusion of certain leading germs and pathogens. Therefore, only hygienically harmless starting materials (including water) and packaging materials may be used for the production and only recognized working techniques may be applied. The GD hygiene guideline and the relevant guidelines for quality assurance of the Federal Chamber of Pharmacists must be observed.

Microbially susceptible extemporaneous preparations should always be protected against microbial spoilage by the addition of a suitable preservative. If preservation is to be excluded, the physician must note this ("Not preserved!"). Contained preservatives must be labeled.

Lack of long-term stability may be responsible for the absence of finished medicinal products containing certain medicinal substances or based on certain dermatic bases, and this may be a major motive for prescribing such extemporaneous preparations. Extemporaneous preparations need only be stable for the intended period of application. In the case of ready-to-use drugs, the shelf life and the period of use by the patient must be distinguished. For ad hoc formulations, however, the prescription, production, dispensing and opening usually coincide so closely that the shelf life before opening, in addition to the use-by date, is practically only relevant for sterile preparations. Prescriptions should be labeled with a specific end date of the use-by date (see NRF, Section I.4., General Information, especially Tables I.4.-2 and I.4.-3), for example: "Do not use after the indicated date".

Drug stock preparations and dermatics bases used in the pharmacy are subject to a different system (see NRF). The use of opened packages of finished medicinal products for formulation purposes in pharmacies must be limited in terms of time; for example, the NRF guideline values for use-by periods from the opening date can be used as an alternative, without, however, exceeding the expiry date of the manufacturer.

Incompatibilities between formulation components and between formulations and their primary packaging materials can be avoided by restricting the use to finished medicinal products and to standardized prescriptions, for example according to SR or NRF. If finished drugs or analogous NRF prescriptions are available, individually composed prescriptions should be prescribed only in specifically justified cases.

When processing drugs in simply composed dermatics bases from recognized and generally accessible regulations (for example from DAB, DAC, SR or NRF), possible incompatibilities can be largely predicted and avoided by switching to alternatives.

Prescriptions based on branded or finished medicinal products should only be prescribed if experimentally validated data on physical, chemical and microbiological quality and shelf life over a period of time appropriate for the intended treatment can be provided by the pharmaceutical manufacturer.

As far as possible in the given context, preference should always be given to formulations that can be found in recognized and generally accessible regulations (for example, in the DAB, DAC, SR, NRF, standard approvals or ADKA regulations).

Extemporaneous preparations must be labeled by the pharmacy in accordance with the ApBetrO. To clarify and supplement the obligatory information mentioned there, it is recommended that the labeling be done in German. The designation of medicinal substances must not be abbreviated or indicated in such a way that the patient or the recipient is misled as to the contents. In the case of externals containing glucocorticoids, "Containing cortisone!" should be indicated.

Physicians and pharmacists should document observations of adverse drug reactions, even with extemporaneous preparations, and report them to the drug commissions. It is recommended that a copy be documented in the pharmacy or physician's office.

Notice. When incorporating ready-to-use dermatics into prescriptions, this process has a significantly increasing effect due to the calculation mechanism of the "Auxiliary Tax for Pharmacies". If the active ingredient is incorporated into an officinal basis of the DAB, DAC or NRF, one can save up to 30% of the price of the finished formulation.

Forms and companies:

• ABDA: ABDA - Federal Association of German Pharmacist Associations
• ADKA: Federal Association of German Hospital Pharmacists
• AKdÄ: Drug Commission of the German Medical Association
• AMG: Medicines Law
• AMK: Drug Commission of the German Pharmacists
• ApBetrO: Pharmacy operating regulations
• BfArM: Federal Institute for Drugs and Medical Devices
• DAB: German pharmacopoeia
• DAC: German Drug Codex
• DDG: German Dermatological Society
• GD: GD Society for Dermopharmacy
• NRF: New formulation form
• SR: standard formulations 1990 (GDR)
• Standard marketing authorisations: Collection of monographs on medicinal products according to § 36 AMG, which are exempted from the obligation of individual authorisation
• ZL: Central Laboratory of German Pharmacists

1. ABDA - Bundesvereinigung Deutscher Apothekerverbände (Ed.), New Prescription Form (NRF), Chapter General Information, Figure I.5.-1 as well as Tables I.2.-1, I.4.-2, I.4.-3 and I.6.-1. Govi-Verlag, Eschborn / Deutscher Apothekerverlag, Stuttgart
2. Hygiene guideline for the production of non-sterile pharmaceutical preparations in pharmacies of 19 January 2000 in the version of 25 November 2002, GD department "Extemporaneous Preparations", www.gd-online.de
3. Meigel WN, Altmeyer P, Jahn S and the DDG-commission "Magistral Recipes" (1997) recommendations on "Magistral Recipes". Dermatologist 48: 702
4. Wolf G (2013) Poöypragmasia in formulations. dermatologist 65: 478-479