1 Department of Pharmacology Drug dosage forms and routes of administration Information about drugs Drug legislation in CZ What is a dosage form? It is a final form, in which the drug is given to the patient. Dosage Form • Mixture of substances with therapeutical effect and excipients • Excipients: antioxidants, fillers, pigments (dyes), fragrances, ointment bases, solvents etc. • No pharmacological effect • Allergies (parabens), intolerance (lactose) • Shape and characteristics of a medical preparation • Adjusted to the route of administration • Influence pharmacokinetics of a medical substance Generations of dosage forms: 1st = classic dosage forms 2nd = controlled release 3rd = controlled biodistribution Excipients of AERIUS tablets: Core: calcium hydrogen phosphate dihydrate, microcrystalline cellulose, maize starch, talc. Coating: lactose monohydrate, hypromellose, titanium dioxide, macrogol 400, indigotin, carnauba wax, white wax. Classification of Dosage Forms According to the consistency: • solid • semi-solid • liquid • gaseous According to the usage: • for internal use (Ad usum internum, e.g. Peroralia, Parenteralia) • for other use (Ad usum alium, e.g. Ocularia, Nasalia, Unguenta). Liquid Dosage Forms a) For internal use: 1. (Per)oral liquids – solutions, suspension, emulsion for per os administration – tinctures, drops, syrups 2. Parenteral liquids – injections – infusions b) For external use: – eye drops, ocular waters, ear drops, nasal drops – liquids for cutaneous use, for compresses – liquids applied to the mucosa (douche – irrigation, gargle) Semi-solid Dosage Forms ⚫ Applied on the skin or mucosa ⚫ Local effect (dermatology) ⚫ Systemic effect (TTS) ⚫ Ointment (unguent) ⚫ Creme ⚫ Gel (jelly) ⚫ Paste ⚫ Transdermal patch (TTS, Emplastra) Solid Dosage Forms Specific in shape: ⚫ Tablet ⚫ Suppository ⚫ Vaginal pessary (suppository) ⚫ Capsule ⚫ Lozenge (pastilles) Non-specific in shape: ⚫ Dusting powder ⚫ Herbal mixture ⚫ Peroral powder: • Classic • Grained • Effervescent Tablets and Capsules Tablets: • Uncoated • Coated • Gastro-resistant • Effervescent • Tablets disperged in the mouth • Chewable • Sublingual • etc. Capsules: • Hard • Soft • Gastro-resistant • With modified release • etc. Gaseous Dosage Forms = Aerodispersions Topical • ear, nasal, oral, sublingual and cutaneous spray Preparations for inhalation • liquids (scattering of liquid drops) • powders (particle size determines the place of absorption) Foams • cutaneous, rectal, vaginal foams Making of an aerodispersion: • Mechanically by a nebulizer (spray) • By liquefied/compressed gas (pressure container) Routes of administration Systemic administration = drug is absorbed into the circulation → it influences all the body • Enterální aplikace: – enteral – parenteral Local (topical) administration = drug is NOT absorbed into the circulation → it affects only the place of application • : – skin, mucosa, e.g. conjunctiva: – GIT, but the drug in not absorbed from GIT How could a drug be administered? Systemic administration – enteral (Per)oral (per os, p.o.) Enteron (ancient greek) = intestine • Onset of effect depends on phys-chem. properties of the medical substance and excipients • Possibility of lower bioavailability: first-pass effect (liver) Rectal (per rectum) • Do not irritate stomach, do not cause nausea • Lower bioavailability – lesser surface of rectum walls • Sooner onset of effect – plexus venosus rectalis flows into vena cava inferior („bypass of the liver“) „First pass“ effect Systemic administration – parenteral Para enteron (ancient greek) = out of the intestine 1. Non-injection (non-invasive) a) oral • Absorption by oral mucosa (e.g. subligual) • Lipophilic substances – quick absorption (2 mins), e.g. nitroglycerin b) inhalation • Gases, vapours nebo small particles • Respiratory diseases (asthma, COPD...) c) transdermal • TTS = transdermal therapeutic system (controlled release) • E.g. hormonal contraception patch, nicotine patch, analgesic patch d) transnasal • Good perfusion of nasal mucosa • Substances could irritate it, or impair cilia function • E.g. calcitonin, antimigraine drugs e) vaginal – e.g. hormonal contraception ring Systemic administration – parenteral 2. Injection (invasive) - non-physiological a) injection • small volume of liquid • i.v. administration – quick onset of effect • i.m., s.c. – gradual absorption into circulation b) infusion • larger volume of liquid • parenteral nutrition, minerals, glucose, ATBs, cytostatics etc. What is this tablet? What is this drug used for? How frequently should I use it? What are possible adverse effects? Who must not use it? What is an appropriate dose? How to store it? Does it influence vigility? Could this drug influence the effect of other drugs? ? ? ? ? ? Information about Drugs PIL & SPC • PIL = patient information leaflet = package leaflet for patients • SPC = summary of product characteristics = information for medical specialists (physicians, pharmacists, nurses etc.) EMA – European Medicine Agency (ema.europa.eu) • Database of RMPs granted central authorisation by EC/EMA • Reports concerning drugs‘ safety – alerts • List of newly authorized drugs SUKL – State Institute for Drug Control (sukl.eu) • Database of RMP authorized in CZ • Free access to all PILs and SPCs (in czech) European Pharmacopoeia = european standard for the quality of drugs (Czech Pharmacopoeia = text from EP + czech specialities) Computer databases of medical preparations • AISLP (czech↔english, in most pharmacies and doctor‘s offices) Pharmacopoeia • Purpose: to guarantee safe, effective and quality drugs • Information about medical substances, excipients, dosage forms • Instructions for production, preparation, control, storage of drugs • Used mostly in pharma industry What could we found there? • Analytical and instrumental examination methods • Materials for drug containers and cases • Instructions to ensure sterility of medical preparations • Instructions concerning radiopharmaceuticals, vaccines etc. • Monographs of specific substances • Tables with usual dosage of drugs in adults, children, animals • etc. NO: mechanism of actions, adverse effects, pharmacokinetics, contraindications, pregnancy safety etc.! Basic Drug Legislation in CZ Act No. 378/2007 Coll., on pharmaceuticals • Research • Authorization of new drugs („registration“) • Production, preparation and distribution • Prescribing and dispense of medical preparations • Destroying of unusable drugs • Pharmacy duties • Pharmacovigilance = drug safety service • Controls and sanctions TYPES OF MEDICINAL PRODUCTS Medicinal products RMP IPP Rx OTC Restricted distribution OTC Fully imbursed Partially imbursed Not imbursed Manufacturing / Preparation Dispensation Reimbursement from health insurance Paper „dispatch note“ e-Rp by sms e-Rx TYPES E-mail e-Rp App e-Rx on ID card PAPER Rx • Exceptional, only in justified cases • Not for repeated use • Pharmacist needs to digitalize it – record into the e-Rx system • Only 1 type of medicine • Valid without doctor‘s stamp, but the identification of the doctor need to be present („IČZ“ – identification number of medical facility) • Which situations can justify the use of paper Rx? • Obligatory – specified addictive substances (Rx „with blue strip“) OVERVIEW OF RX VALIDITY • e-Rx – 14 days + day of issue – Doctor can extend validity up to 1 year, pharmacist can add another 14 days • Emergency – end of the day following the day of issue • Rx for repeated use – 6 months, max 1 year • Paper Rx – 14 days + day of issue • Rx „with blue strip“ – 14 days + day of issue; extension up to 30 days Medical Prescription (Rx) in CZ ADDICTIVE SUBSTANCES • Prescription according to the substance classification (Gov. Reg. No. 463/2013, on the List of addictive substances – Appendices 1- 8) Rx „with blue strip“ • Appendix 1 + 5 = narcotics (list I), psychotropics (list II) specified in Single Convention on Narcotic Drugs (1961), and Convention on Psychotropic Substances (1971) • Rx is a paper form, 3 pages (1 original, 2 copies) • 1 Rx = 1 type of medicine • Specimen of the form is stated in legislation • Validity 14 days + day of issue Legislation – Drugs of Abuse