Drug delivery approaches, routes of administration, prolonged release preparations. PharmDr. Ondřej Zendulka, Ph.D. Drug delivery approaches 1.Drug dosage forms – review. 2.Routes of administration. 3.Innovations in drug delivery. > Drug dosage form • final form, in which is drug administerd to patient • inlfuences mainly pharmacokinetic properties of administered drug Classification with regard to: • consistence • solid • semi-solid • liquid • gaseous • administration site (internal/external use) • shape (specific/nonspecific) • number of active substances (one or more) Drug delivery approaches 1.Drug dosage forms – review. 2.Routes of administration. 3.Innovations in drug delivery. > Drug delivery approaches local effect systemic external administration enteral internal parenteral Drug delivery approaches Administration Systemic • drug is absorbed to systemic circulation • possible influence on whole body • higher risk of AE • Local • drug absorption is limited • effect aimed on target tissue/organ • low risk of AE • CSF Schema of systemic administration Systemic circulation liver skin muscle placenta lungs brain gut foetus bone milk, sweat glands kidney joint enteral transdermal intravascular intraosseal intrathecal intramuscular intraarticular inhalation bile milk, sweat stool urine expired air modified from Rang &Dále‘s Pharmacology 2011 Drug delivery approaches Administration EXTERNAL • administration on skin, mucosas or to body cavities • • effect local/systemic • INTERNAL • administration other than on skin, mucosas or to body cavities • • effect local/systemic • External administration Epicutaneous Conjunctival Intranasal Inhalation Rectal Vaginal sublingual, intraurethral, dental, gingival, oral, endotracheopulmonal, intraaural…. Epicutaneous administration •Local effect •ointments, creams, solutions, patches •minimal AE •dermatology •Systemic effect •transdermal administration •mainly patches •continuous release •local+systemic AE •high compliance •easy discontinuation převzato z: Hock & Pfister, Pharm Sci Tech Tod, 2, 1999 Conjunctival administration •usually eye drops and ointments •local effect •risk of systemic AE •specific quality requirememnts •drops, sprays, ointment •local effect - antiseptics, ATB - antihistamines, decongestants - antiflogistics •systemic effect - analgesics, antivirotics - hormones (ADH, gonadotropin, insulin) Intranasal administration Inhalation •gases, aerosols •systemic effect – general anesthetics •local effect – antiasthmatics •fast onset of effect •minimal presystemic elimination •administration from spray cans or other instruments (turbohaler, dischaler, nebulizator) Rectal administration •suppositories, capsules, tablets, foams, tampones •alternative for peroral administration •variable absorption Internal administration Enteral-peroral 1. for local effect • minimal AE • risk of interaction with coadministered drugs Internal administration Enteral-peroral 2. for systemic effect • drug absorbed from different parts of GIT •can be influenced by DDF • „slow“ effect onset • the effect depends on patients „compliance“ Enterální LF s řízeným uvolněním • systems of controlled release: matrix reservoirs particles nanoparticles • controlled release: continuous pulsatile •1952 Spansules™ Parenteral 1. local effect • i.v. or e.v. • injections or implantation • restriction of absorption = effect prolongation + decrease of AE risk Internal administration Parenteral 2. systemic effect • i.v. x e.v. • pharmacokinetic differences • specific qualitative requirements • implants Internal administration Parenteral 2. sytsemic effect • intravenous/intraarterial • subcutaneous • intramuscular • intradermal • intrathecal • intraarticular, intraoccular, intraosseous Internal administration • intrathecal Internal administration •intraarticular •intraocular •intraosseous Internal administration Implants • degradable/nondegradable • usually s.c. or intraocular • systemic/local effect • continuous/pulsatile release • compliance • complicated discontinuation Internal administration Drug delivery approaches Factors influencing the drug delivery approach: • drug physicochemical properties • therapeutic indication + disease phase • benefit:risk ratio • co-morbidities, co-medications Drug delivery approaches 1.Drug dosage forms – review. 2.Routes of administration. 3.Innovations in drug delivery. > Transdermal delivery 3. generation of passive patches • drug in the adhesive layer • decreased irritation • decreased drug concentration • size decrease Active transdermal preparations • in the phase of clinical trials • physical principles enhancing or controling drug release Transdermal administration Patches with microneedles • even macromolecular substances can be delivered • immunization, vaccination • rather intradermal than transdermal Liposomes •particle systems •both lipophilic and hydrophilic substances •biocompatible, degradable •cen be used for drug targeting Nanoparticles •size 1-1000 nm •structure: nanospheres x nanocapsules •degradable, nontoxic •highly variable •smart nanoparticles Thank you for your attention.