Nasal/Sublingual/Buccal Drug Delivery PDF

1103-511 Pharmaceutics III NASAL/SUBLINGUAL/BUCCAL DRUG DELIVERY Mutasem (Mark) Rawas-Qalaji B. Pharm (Hon.), Ph.D. Associate Professor Department of Pharmaceutics & Pharmaceutical Technology College of Pha...

1103-511 Pharmaceutics III NASAL/SUBLINGUAL/BUCCAL DRUG DELIVERY Mutasem (Mark) Rawas-Qalaji B. Pharm (Hon.), Ph.D. Associate Professor Department of Pharmaceutics & Pharmaceutical Technology College of Pharmacy 1 University of Sharjah  - both local and systemic + brain delivery Nasal – Anatomy & Physiology Nasal cavity consists of 3 regions: (total absorption area don't give all that 75-90 cm2/nostril, 20 mL capacity, 53 µm thick) - we easy absorption ↳ we administerdrops ↳ very thin → – Vestibule: just inside the nostrils, covered with stratified squamous epithelium and hairs – Olfactory: at the roof of the nasal cavity – Respiratory: contains turbinates, covered with pseudostratified columnar epithelium, which is covered with microvilli and cilia propel towards the GIT (4-6 µm long and beat with 1000 strokes/min → mucous layer is - propelled backward into GIT at a rate of 5 mm/min → mucous gets renewed every 15-20 min) → mucociliary clearance mechanism→ → short residence time anjiñi ig The function of the nasal cavity is to filter, warm, and The hair of nose in the nose humidify the inhaled air; and to trap the inhaled particles and microorganisms by the hair in the nasal vestibule or by the mucous layer in the respiratory area. Drug could be - entrapped in mucous by TM UCOUS could help opposite Max d 20min charges Mutasem Rawas-Qalaji, B. Pharm., Ph.D. PHRC4840 - Dosage Forms & Drug Delivery increase residence time 2 *snort  → highly vascular F. Netter, Atlas of Human Anatomy, 2003 Mutasem Rawas-Qalaji, B. Pharm., Ph.D. 3 PHRC4840 - Dosage Forms & Drug Delivery  Nasal Drug Delivery ↳ short residence time 1. Local delivery (for the treatment of local diseases) – Allergy, congestion, infection – Examples: Beconase AQ® nasal spray (beclomethasone dipropionate) for seasonal allergies http://us.gsk.com/products/assets/us_beconase_aq.pdf Afrin ® nasal spray and drops (Oxymetazole HCl) for congestion Ocean Mist saline d reduce inflammation in the nose → vasoconstrictors cause a local action. 4 Mutasem Rawas-Qalaji, B. Pharm., Ph.D. PHRC4840 - Dosage Forms & Drug Delivery Mutasem Rawas-Qalaji, B. Pharm., Ph.D. PHRC4840 - Dosage Forms & Drug Delivery 5 2. Systemic delivery: – Advantages: Noninvasive and accessible route Rapid absorption and onset of action (high vascular area)thin membrane Cthinner than sublingual) + + permeable Increase drug bioavailability nature Avoid GIT degradation and first pass metabolism – Disadvantages: smaller absorption area Absorption barriers 1- mucous clearance mechanism Nasal irritation and mucosal damages Small absorption area SL used more than is Mutasem Rawas-Qalaji, B. Pharm., Ph.D. PHRC4840 - Dosage Forms & Drug Delivery the nasal 6 – Routes of systemic absorption: Absorption form the nasal cavity, examples: – Amyl Nitrate vials for inhalation (for treatment of emergency anginal pain) >>> recreational abuse - very large molecule passes → – Miacalcin ® spray (Calcitonin) for osteoporosis ✓ by passive advantage diffusion (Miacalcin spray, Novartis) of nasal drug delivery t – Imetrix ® spray (Sumatriptan) and Zomig ® spray (Zolmitriptan) for because of migraine (Imetrix spray, GSK) rich vasculature – FluMist ® (influenza virus vaccine live) for active immunization against influenza A and B viruses (http://www.flumist.com/) not target is lung Absorption from the respiratory systems → nose (bronchial tree and lungs) through the nasal and oral cavities for both local and systemic effect →→→ Pulmonary Drug Delivery – Afrezza® Inhaled Insulin (https://www.afrezza.com/) (http://www.medpagetoday.com/Cardiology/Type1Diabetes/55663 ) Mutasem Rawas-Qalaji, B. Pharm., Ph.D. PHRC4840 - Dosage Forms & Drug Delivery 7  in market still no drugs → 3. Delivery to the brain: Investigational → roof of the nose – The olfactory mucosa (smelling area in nose) is in direct contact with the brain and CSF. – Medications absorbed across Olfactory mucosa, nerve the olfactory mucosa may directly enter the CSF. Brain – Absorption depends on the t its hard for CSF sprays physiochemical properties of to hit that area in the nose olfactory [ the drug (similar to systemic ) mucosa , nerve delivery) A. absorption is usually rapidHighly vascular nasal mucosa Example: Mystic Pharm, Inc and permeability is fast Shin Nippon Biomedical Lab mate it - positively charged → + residence → we need to prepare formulation in a way to emanate adhesion and increase contact time Mutasem Rawas-Qalaji, B. Pharm., Ph.D. PHRC4840 - Dosage Forms & Drug Delivery Until its absorbed 8.  Adhesion and permeation of drug can be achieved by : ① reducing the particle size C nanoparticles) ② Maco adhesive properties ( proteins in the cell membrane are if negatively charged , so we have a formulation with positive charge , it can adhere for a longer period and have a better chance of permeating ]. ③ of the properties drug molecules permeate → to , it has to have good lipophilicity + good water solubility to dissolve in body fluids and reach the site of absorption.  clearance major challenge mucociliary : mechanism the reason why we dont see alot of drugs as nasal due to low dose and irritation Nasal Absorption Barriers d lowresidena tnesemble Ill times we need tote Physiochemical properties of the drug (typical for all routes) residence time – Molecular weight and size. Mucosal Interstitial – Partition coefficient (lipophilicity) Mucosal membrane epithelial cell fluid Blood vessel Nasal physiological barriers Lateral space conc gradient moves it – Mucociliary clearance mechanism (15-20 min) better – Membrane permeability thenosenasa → chance toaliowdnegtopermealemucneasier Transcellular passive diffusion (lipophilic and low Mwt drugs) very – Almost similar to IV, e.g. fentanyl nasal bioavailability ~80%, Tmax ~7 rapid min iesspotefmtigatfaorsprlfehf efficient ddosetothelooy that we - -. overcome Paracellular transport (polar and low Mwt drugs