Adobe Systems Dpt. of Pharmacology, Faculty of Medicine, MU 1 Drug delivery approaches. Ondřej Zendulka [USEMAP] Adobe Systems Structure of the lecture 1.Classification of administration routes 2.Factors related to administration route selection 3.Characteristic of administration routes 4.Innovative administration routes 2 [USEMAP] Adobe Systems Local • drug absorption is limited • effect aimed on target tissue/organ • low risk of AE • effect depends upon final concentration Administration/effect of drug Systemic • drug is absorbed to systemic circulation • possible influence on whole body • higher risk of AE • effect depends on dose, bioavailability and DDF ̶ 3 [USEMAP] Adobe Systems Classification of administration routes 4 local type of effect systemic parenteral enteral enteral parenteral transdermal, transnasal, i.v., i.m., s.c., i.a., inhalations, i.o…. epicutaneous, vaginal, intraocular, intraarticular, intrathecal… peroral, rectal, gastric peroral, rectal, gastric [USEMAP] Adobe Systems Classification of administration routes Non-invasive • vaginal, (intrauterine?) • sublingval • epicutaneous • oral • intranasal • inhalational • rectal •… Invasive •intravenous • intraartrerial • intraoseal • intramuscular • subcutaneous • intradermal • implants •… •with regard to the disruption of natural protective barriers 8 [USEMAP] Adobe Systems Classification of administration routes Intermitent use • repeated use • plasma level fluctuation • all administration routes • local and systemic use Continuous use • constant speed of drug administration = constant plasma level of drug • intravenous • intramuscular • subcutaneous/implants • intravaginal/intrauterine • intrathecal • transdermal •with respect to administration schedule 8 Adobe Systems Physical-chemical properties of drug • lipophilicity/hydrophilicity, solubility • chemical structure/size of molecule • pH/pKa • availability of pharmaceutical form 7 Adobe Systems Therapeutic indication + severity of disease • the same drug administered differentialy with respect to diagnosis • local administration prefered • acute situations – fast onset of effect required Benefit:risk ratio • the more severe, the „more risky“ administration 8 [USEMAP] Adobe Systems Comorbidities • can block distinct administration routes • can influence drugs efficacy Comedication • risk of drug-drug interactions 9 Adobe Systems Administration routes - local effect •intraurethral, intravesical, intracavernal •dental, gingival •endotracheopulmonal 18 Adobe Systems Administration routes - local effect •intraaural •intraamniotic •intracoronar, intraarterial 18 Adobe Systems Ocular/conjunctival administration • usually eye drops and ointments • local effect • risk of systemic AE • specific quality requirements - sterility 19 Intraocular administration •intravitreal implants and injections in macular degeneration [USEMAP] Adobe Systems Intrathecal/intracerebral/intracerebroventricular administration • to the subarachnoideal space /brain/ brain ventricles 20 Adobe Systems Intraarticular administration •analgesics/antiphlogistics •hyaluronic acid •for local effect 21 [USEMAP] Adobe Systems Administration routes for local and systemic effect •vaginal, intrauterinne •dermal/transdermal •intranasal/transnasal •inhalational •rectal •oral/transbucal, sublingual •peroral 22 [USEMAP] Adobe Systems Vaginal, endocervical, intrauterinal •1. local effect • minimum of AE • specific adjuvants ↓ pH • antibiotics, antimycotics, antiparasitics • 2. systemic effect • vaginal rings intrauterine devices • controlled drug release • contraceptives ̶ 23 [USEMAP] Adobe Systems Epicutaneous/transdermal 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 23 Adobe Systems Intranasal/transnasal administration •drops, sprays, ointments •local effect - antiseptics, ATB • - antihistamines, decongestants • - antiphlogistics •systemic effect - analgesics, antivirotics • - hormones (ADH, gonadotropin, insulin) 25 Adobe Systems 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, nebuliser) 26 Adobe Systems Rectal administration •suppositories, capsules, tablets, foams, tampones •alternative for peroral administration in case of nausea/vomitting or unconciousness •variable drug absorption 27 [USEMAP] Adobe Systems Oral/sublingual/buccal administration •fast onset of systemic effect •oinly for small and lipophilic molecules •sprays, tablets, dispergable films •analgesics – fentanyl, buprenorfin •hypnotics – zolpidem •vasodilators – nitroglycerine •antiemetics – ondansetrone •homeopatics, alergens, cannabis…. 28 Adobe Systems Peroral administration 1. for local effect • minimal AE • risk of interaction with coadministered drugs •antacids, laxatives, antibiotics 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“ Salvador et al. 2017 28 Adobe Systems Administration routes for mainly systemic effect •intravenous/intraosseous •intramuscular •subcutaneous injections and implants • 30 [USEMAP] Adobe Systems Injections intravenous, (intraarterial) •injection/infusion •100% bioavailability, „immediate“ effect •true solutions + emulsions intramuscular •max. volume 5 ml •to m. glu. maximus •absorption: solution> emulsion> suspension subcutaneous •to 2 ml •variable absorption with regard to adipose tissue 31 Adobe Systems Injections intradermal •minimal volume •diagnostic purposes intraosseal •alternative to i.v. •injection/infusion §Eg. Atropine onset of the effect §i.v. 30-90 s; s.c. 15-30 min; i.m. 30-45 min 32 [USEMAP] Adobe Systems Implants • degradable/nondegradable • usually s.c. or intraocular • systemic/local effect • continuous/pulsatile release = continuous/repeated drug administration • increased patient‘s compliance • complicated discontinuation • 33 Adobe Systems Innovations in drug administration •new posssibilities of administration routes are probably depleted => modification of DDF •the goals are: 1. increase of drug safety/decrease of drug toxicity 2. increase the efficacy of administered dose 3. increase the patient‘s compliance 35 [USEMAP] Adobe Systems More about innovations in drug administrations: •Current Opinion in Pharmacology, Vol. 36, 2017 36 [USEMAP]