DOCSLIB.ORG

Strategies to Enhance Drug Absorption Via Nasal and Pulmonary Routes

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Strategies to Enhance Drug Absorption Via Nasal and Pulmonary Routes pharmaceutics Review Strategies to Enhance Drug Absorption via Nasal and Pulmonary Routes Maliheh Ghadiri * , Paul M. Young and Daniela Traini Respiratory Technology, Woolcock Institute of Medical Research and Discipline of Pharmacology, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, Australia; [email protected] (P.M.Y.); [email protected] (D.T.) * Correspondence: [email protected]; Tel.: +61(2)911-40366 Received: 16 January 2019; Accepted: 5 March 2019; Published: 11 March 2019 Abstract: New therapeutic agents such as proteins, peptides, and nucleic acid-based agents are being developed every year, making it vital to find a non-invasive route such as nasal or pulmonary for their administration. However, a major concern for some of these newly developed therapeutic agents is their poor absorption. Therefore, absorption enhancers have been investigated to address this major administration problem. This paper describes the basic concepts of transmucosal administration of drugs, and in particular the use of the pulmonary or nasal routes for administration of drugs with poor absorption. Strategies for the exploitation of absorption enhancers for the improvement of pulmonary or nasal administration are discussed, including use of surfactants, cyclodextrins, protease inhibitors, and tight junction modulators, as well as application of carriers such as liposomes and nanoparticles. Keywords: nasal; pulmonary; drug administration; absorption enhancers; nanoparticle; and liposome 1. Background Absorption enhancers are functional excipients included in formulations to improve the absorption of drugs across biological barriers. They have been investigated for many years, particularly to enhance the efficacy of peptides, proteins, and other pharmacologically active compounds that have poor barrier permeability [1]. The ideal absorption enhancer should be one that protects biological agents against enzymatic degradation and causes a rapid opening of the relevant barrier while enhancing absorption transiently. As a portal for non-invasive delivery, nasal and pulmonary administration has several advantages over traditional oral medication or injection. Nasal and pulmonary delivery are non-invasive routes of administration that target the delivered dose directly to the site of drug action [2,3]. Moreover, drug delivery to the respiratory area can also be used for systemic delivery of peptides and proteins due to the large surface area for drug absorption. Pulmonary and nasal administration bypasses first-pass metabolism that is observed in oral administration and the lung and nasal cavity have a low drug metabolizing environment [4]. Despite all these advantages, there is a significant challenge to enhance the absorption of the active agent via these routes. In nasal and pulmonary administration, absorption enhancers have been investigated over the last two decades, to increase the rate of absorption by targeting different mechanisms [5,6]. These mechanisms are either to improve the permeation of materials across the epithelial barrier via intracellular or paracellular mechanisms (Figure1) or to enhance stability and mucus solubility of the drugs regionally. However, to date, no safe absorption enhancer for pulmonary administration of drugs has translated into commercial products. Their use has generated safety concerns due to potential irreversible alteration of the epithelial cell membrane, which could potentially make the lung susceptible to the entry of exogenous allergens. While there are Pharmaceutics 2019, 11, 113; doi:10.3390/pharmaceutics11030113 www.mdpi.com/journal/pharmaceutics PharmaceuticsPharmaceutics2019 2019,,11 11,, 113 x FOR PEER REVIEW 22 of 2020 of the epithelial cell membrane, which could potentially make the lung susceptible to the entry of noexogenous absorption allergens. enhancers While for there pulmonary are no drugabsorption administration enhancers on for the pulmonary market, quite drug a administration few appear to beon atthe the market, threshold quite of a becoming few appear products to be at for the nasal thresh administration.old of becoming products for nasal administration. ThisThis reviewreview criticallycritically assessesassesses advancesadvances inin thethe fieldfield ofof absorptionabsorption enhancersenhancers forfor nasalnasal andand pulmonarypulmonary drugdrug administration.administration. The The various various agents used to increase the absorptionabsorption ofof poorlypoorly permeablepermeable drugs,drugs, theirtheir mechanismsmechanisms ofof action,action, safety,safety, and and effectiveness effectiveness are are also also presented. presented. FigureFigure 1.1. MechanismsMechanisms ofof absorption absorption includes; includes; (a) (a) Transcellular Transcellular diffusion, diffusion, (b) (b) Para Para cellular cellular transport, transport, (c) Vesicle(c) Vesicle mediated mediated transport, transport, and an (d)d Carrier(d) Carrier mediated mediated transport. transport. 2.2. TheThe BarriersBarriers TheThe firstfirst requirement requirement for for drug drug absorption absorption is for is thefor activethe active pharmaceutical pharmaceutical ingredient ingredient (API, or(API, drug) or todrug) reach to the reach absorbing the absorbing barrier. barrier. For the For respiratory the respiratory system, system, the drug the has drug to be has deposited to be deposited on the luminal on the surfaceluminal of surface the epithelial of the membraneepithelial membrane and be absorbed and be before absorbed being before cleared being or degraded. cleared Furthermore,or degraded. adequateFurthermore, absorption adequate of theabsorption API may of also the requireAPI may controlling also require its releasecontrolling profile its as release it passes profile through as it multiplepasses through biological multiple barriers. biological These barriers barriers. include: These (1)barriers the surfactant include: layer,(1) the mucus surfactant layer, layer, (2) epithelial mucus layer,layer, (3)(2) interstitium epithelial layer, and basement (3) interstitium membrane, and basement and (4) capillary membrane, endothelium and (4) (Figurecapillary2). endothelium (FigureThe 2). mucus layer is the first barrier. The deposited drug needs to be dissolved or transverse the mucusThe layer mucus before layer degradation is the first barrier. due to theThe enzymatic deposited activitydrug needs or clearance to be dissolved by mucociliary or transverse activity. the Becausemucus layer the ciliary before action degradation is relatively due fastto the in removingenzymatic the activity drug fromor clearance the absorption by mucociliary site, permeation activity. enhancersBecause the must ciliary act action rapidly is torelatively increase fast bioavailability. in removing the The drug understanding from the absorption of mucus site, layer permeation thickness andenhancers clearance must rate act is rapidly important to increase to develop bioavailab drug deliveryility. The strategies understanding to overcome of mucus mucosal layer clearancethickness mechanisms.and clearance In rate the is lung, important the thickness to develop of the drug luminal delivery mucus strategies gel has been to overcome reported tomucosal be ~5–10 clearanceµm [7]. Themechanisms. underlying, In the less lung, viscoelastic the thic solkness layer, of the also luminal known mucus as the periciliarygel has been liquid, reported covers to thebe ~5–10 cilia andμm has[7]. anThe additional underlying, 5–10 lessµ mviscoelastic thickness sol [7]. layer, However, also known other studiesas the periciliary based on liquid, confocal covers fluorescence the cilia microscopyand has an additional suggest that 5–10 airway μm thickness mucus may [7]. range However, in thickness other studies from 5 based to 55 µonm confocal [8,9]. The fluorescence nasal tract hasmicroscopy a thin mucus suggest layer that which airway is mucus readily may accessible range in and thickness considered from highly5 to 55 permeableμm [8,9]. The compared nasal tract to otherhas a mucosalthin mucus surfaces layer [which10]. In is the readily nasal accessibl tract, thee ciliaryand considered motion transports highly permeable mucus with compared the flow to rateother of mucosal about 5 mmsurfaces per minute,[10]. In the and nasal the mucus tract, the layer ciliary is renewed motion approximatelytransports mucus every with 20 the min flow [11 ,rate12]. Similarly,of about 5 the mm luminal per minute, gel layer and of respiratorythe mucus tractlayer mucusis renewed is replaced approximately every 10 toevery 20 min, 20 min [11]. [11,12]. While, theSimilarly, sol layer the of luminal respiratory gel layer mucus of hasrespiratory a slower tract rate mucus of clearance is replaced than theevery more 10 to solid-like 20 min, luminal[11]. While, gel layer.the sol Drug layer absorption of respiratory via mucus the nose has is a dependent slower rate on of drug clearance clearance than fromthe more the nasalsolid-like cavity, luminal which gel is determinedlayer. Drug byabsorption nasal mucociliary via the nose clearance is dependent (MC). In on a studydrug clearance by Inoue from et al., the the nasal effect cavity, of nasal which MC on is indetermined vivo absorption by nasal of mucociliary norfloxacin afterclearance intranasal (MC). administration In a study by Inoue to rats et was al., the estimated effect of quantitatively. nasal MC on Thisin vivo study absorption resulted of in norfloxacin a model to after precisely
Load more

Recommended publications
  • Intranasal and Rectal Diazepam for Rescue Therapy: Assessment of Pharmacokinetics and Tolerability a Dissertation Submitted to T
    INTRANASAL AND RECTAL DIAZEPAM FOR RESCUE THERAPY: ASSESSMENT OF PHARMACOKINETICS AND TOLERABILITY A DISSERTATION SUBMITTED TO THE FACULTY OF THE GRADUATE SCHOOL OF THE UNIVERSITY OF MINNESOTA BY VIJAY DEEP IVATURI IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY ADVISER: JAMES. C. CLOYD DECEMBER 2010 © VIJAY DEEP IVATURI 2010 ACKNOWLEDGEMENTS This thesis was carried out at the Center for Orphan Drug Research, Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, United States. I would like to thank the following persons who have all contributed to this thesis and have been important to me throughout my time as a research student; My supervisor/adviser Professor James Cloyd for giving me the opportunity to join the Orphan Drug Research group. Thank you for sharing your vast knowledge and enthusiasm about research. Thanks for all the care and consideration that you and Mrs. Cloyd have always shown and for letting me experience a family away from home. I also appreciate you letting me pursue my personal interest in the application of Pharmacometrics into our research projects and for letting me take a break from my studies to go to GlaxoSmithKline and try a world outside the university. My second committee member Dr. Robert Kriel for showing interest in my work and always questioning the usability and necessity of things and for also being the first to give comments back on reports and manuscripts. Thanks for sharing your expert clinical knowledge and giving me an opportunity to do a clinical clerkship at Hennipen County Medical Center and Gillette Children’s Hospital.
    [Show full text]
  • Intranasal Drug Delivery System- a Glimpse to Become Maestro
    Journal of Applied Pharmaceutical Science 01 (03); 2011: 34-44 Received: 17-05-2011 Revised on: 18-05-2011 Intranasal drug delivery system- A glimpse to become Accepted: 21-05-2011 maestro Shivam Upadhyay, Ankit Parikh, Pratik Joshi, U M Upadhyay and N P Chotai, ABSTRACT Intranasal drug delivery – which has been practiced for thousands of years, has been given a new lease of life. It is a useful delivery method for drugs that are active in low doses and Shivam Upadhyay, Ankit Parikh, Pratik show no minimal oral bioavailability such as proteins and peptides. One of the reasons for the low Joshi, N P Chotai, Dept of Pharmaceutics, A R Collage of degree of absorption of peptides and proteins via the nasal route is rapid movement away from the Pharmacy, V.V.Nagar, Gujarat,India. absorption site in the nasal cavity due to the Mucociliary Clearance mechanism. The nasal route circumvents hepatic first pass elimination associated with the oral delivery: it is easily accessible and suitable for self-medication. The large surface area of the nasal mucosa affords a rapid onset of therapeutic effect, potential for direct-to-central nervous system delivery, no first-pass metabolism, and non-invasiveness; all of which may maximize patient convenience, comfort, and compliance. IN delivery is non -invasive, essentially painless, does not require sterile preparation, U M Upadhyay and is easily and readily administered by the patient or a physician, e.g., in an emergency setting. Sigma Institute of Pharmacy, Baroda, Furthermore, the nasal route may offer improved delivery for “non-Lipinski” drugs.
    [Show full text]
  • Nasal Delivery of Aqueous Corticosteroid Solutions Nasale Abgabe Von Wässrigen Corticosteroidlösungen Administration Nasale De Solutions Aqueuses De Corticostéroïdes
    (19) TZZ _¥__T (11) EP 2 173 169 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: A01N 43/04 (2006.01) A61K 31/715 (2006.01) 21.05.2014 Bulletin 2014/21 (86) International application number: (21) Application number: 08781216.0 PCT/US2008/068872 (22) Date of filing: 30.06.2008 (87) International publication number: WO 2009/003199 (31.12.2008 Gazette 2009/01) (54) NASAL DELIVERY OF AQUEOUS CORTICOSTEROID SOLUTIONS NASALE ABGABE VON WÄSSRIGEN CORTICOSTEROIDLÖSUNGEN ADMINISTRATION NASALE DE SOLUTIONS AQUEUSES DE CORTICOSTÉROÏDES (84) Designated Contracting States: • ZIMMERER, Rupert, O. AT BE BG CH CY CZ DE DK EE ES FI FR GB GR Lawrence, KS 66047 (US) HR HU IE IS IT LI LT LU LV MC MT NL NO PL PT • SIEBERT, John, M. RO SE SI SK TR Olathe, KS 66061-7470 (US) (30) Priority: 28.06.2007 PCT/US2007/072387 (74) Representative: Dörries, Hans Ulrich et al 29.06.2007 PCT/US2007/072442 df-mp Dörries Frank-Molnia & Pohlman Patentanwälte Rechtsanwälte PartG mbB (43) Date of publication of application: Theatinerstrasse 16 14.04.2010 Bulletin 2010/15 80333 München (DE) (73) Proprietor: CyDex Pharmaceuticals, Inc. (56) References cited: Lenexa, KS 66214 (US) WO-A1-2005/065649 US-A1- 2006 194 840 US-A1- 2007 020 299 US-A1- 2007 020 330 (72) Inventors: • PIPKIN, James, D. Lawrence, KS 66049 (US) Note: Within nine months of the publication of the mention of the grant of the European patent in the European Patent Bulletin, any person may give notice to the European Patent Office of opposition to that patent, in accordance with the Implementing Regulations.
    [Show full text]
  • Scope and Limitations on Aerosol Drug Delivery for the Treatment of Infectious Respiratory Diseases Hana Douafer, Jean Michel Brunel, Véronique Andrieu
    Scope and limitations on aerosol drug delivery for the treatment of infectious respiratory diseases Hana Douafer, Jean Michel Brunel, Véronique Andrieu To cite this version: Hana Douafer, Jean Michel Brunel, Véronique Andrieu. Scope and limitations on aerosol drug delivery for the treatment of infectious respiratory diseases. Journal of Controlled Release, Elsevier, 2020, 325, pp.276-292. 10.1016/j.jconrel.2020.07.002. hal-03084998 HAL Id: hal-03084998 https://hal.archives-ouvertes.fr/hal-03084998 Submitted on 8 Jan 2021 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Scope and limitations on aerosol drug delivery for the treatment of infectious respiratory diseases Hana Douafer, PhD1, Véronique Andrieu, PhD2 and Jean Michel Brunel, PhD1* Corresponding Author: Jean-Michel Brunel, PhD 1 Aix Marseille Univ, INSERM, SSA, MCT, 13385 Marseille, France. E-mail : [email protected]. Phone : (+33) 689271645 2Aix Marseille Univ, IRD, APHM, MEPHI, IHU Méditerranée Infection, Faculté de Médecine et de Pharmacie, 13385 Marseille, France. Abstract: The rise of antimicrobial resistance has created an urgent need for the development of new methods for antibiotics delivery to patients with pulmonary infections in order to mainly increase the effectiveness of the drugs administration, to minimize the risk of emergence of resistant strains, and to prevent patients reinfection.
    [Show full text]
  • Intranasal Medication Administration – Adult/Pediatric – Inpatient/Ambulatory/Primary Care Clinical Practice Guideline
    Intranasal Medication Administration – Adult/Pediatric – Inpatient/Ambulatory/Primary Care Clinical Practice Guideline Note: Active Table of Contents – Click to follow link Executive Summary ................................................................................................................................ 3 Scope ..................................................................................................................................................... 7 Methodology ......................................................................................................................................... 7 Definitions ............................................................................................................................................. 8 Introduction ........................................................................................................................................... 8 Recommendations ................................................................................................................................. 9 General Recommendations for Intranasal Administration ....................................................................... 9 Drug-Specific Practice Recommendations ............................................................................................. 10 UW Health Implementation ................................................................................................................. 14 Appendix A. Evidence Grading Scheme ................................................................................................
    [Show full text]
  • First Clinical Trials of the Inhaled Enac Inhibitor BI 1265162 in Healthy Volunteers
    Early View Original article First clinical trials of the inhaled ENaC inhibitor BI 1265162 in healthy volunteers Alison Mackie, Juliane Rascher, Marion Schmid, Verena Endriss, Tobias Brand, Wolfgang Seibold Please cite this article as: Mackie A, Rascher J, Schmid M, et al. First clinical trials of the inhaled ENaC inhibitor BI 1265162 in healthy volunteers. ERJ Open Res 2020; in press (https://doi.org/10.1183/23120541.00447-2020). This manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Copyright ©ERS 2020. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0. First clinical trials of the inhaled ENaC inhibitor BI 1265162 in healthy volunteers Authors Alison Mackie;1 Juliane Rascher;2 Marion Schmid;1 Verena Endriss;1 Tobias Brand;1 Wolfgang Seibold1 1Boehringer Ingelheim, Biberach an der Riss, Germany. 2SocraMetrics GmbH, Erfurt, Germany, on behalf of BI Pharma GmbH & Co. KG, Biberach an der Riss, Germany Corresponding author: Alison Mackie Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss Germany Email: [email protected] Tel: +49735154145536 Journal suggestion: ERJ Open Research Short title: BI 1265162 in Phase I trials Keywords: Cystic fibrosis, ENaC inhibitor, Phase I, airway surface hydration, mucus clearance Abstract (250 words/250 words permitted) Background: Inhibition of the epithelial sodium channel (ENaC) represents a mutation-agnostic therapeutic approach to restore airway surface liquid hydration and mucociliary clearance in patients with cystic fibrosis.
    [Show full text]
  • Intranasal Pregabalin Administration: a Review of the Literature and the Worldwide Spontaneous Reporting System of Adverse Drug Reactions
    brain sciences Perspective Intranasal Pregabalin Administration: A Review of the Literature and the Worldwide Spontaneous Reporting System of Adverse Drug Reactions Mohamed Elsayed *, René Zeiss, Maximilian Gahr, Bernhard J. Connemann and Carlos Schönfeldt-Lecuona Department of Psychiatry and Psychotherapy III, University of Ulm, Leimgrubenweg 12-14, 89075 Ulm, Germany; [email protected] (R.Z.); [email protected] (M.G.); [email protected] (B.J.C.); [email protected] (C.S.-L.) * Correspondence: [email protected]; Tel.: +49-(0)-731-500-61411; Fax: +49-(0)-731-500-61412 Received: 2 October 2019; Accepted: 11 November 2019; Published: 13 November 2019 Abstract: Background: It is repeatedly reported that pregabalin (PRG) and gabapentin feature a potential for abuse/misuse, predominantly in patients with former or active substance use disorder. The most common route of use is oral, though reports of sublingual, intravenous, rectal, and smoking administration also exist. A narrative review was performed to provide an overview of current knowledge about nasal PRG use. Methods: A narrative review of the currently available literature of nasal PRG use was performed by searching the MEDLINE, EMBASE, and Web of Science databases. The abstracts and articles identified were reviewed and examined for relevance. Secondly, a request regarding reports of cases of nasal PRG administration was performed in the worldwide spontaneous reporting system of adverse drug reactions of the European Medicines Agency (EMA, EudraVigilance database). Results: The literature search resulted in two reported cases of nasal PRG use. In the analysis of the EMA-database, 13 reported cases of nasal PRG use (11 male (two not specified), mean age of users = 34.2 years (four not specified)) were found.
    [Show full text]
  • Achievements in Thermosensitive Gelling Systems for Rectal Administration
    International Journal of Molecular Sciences Review Achievements in Thermosensitive Gelling Systems for Rectal Administration Maria Bialik, Marzena Kuras, Marcin Sobczak and Ewa Oledzka * Department of Biomaterials Chemistry, Chair of Analytical Chemistry and Biomaterials, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha St., 02-097 Warsaw, Poland; [email protected] (M.B.); [email protected] (M.K.); [email protected] (M.S.) * Correspondence: [email protected]; Tel.: +48-22-572-07-55 Abstract: Rectal drug delivery is an effective alternative to oral and parenteral treatments. This route allows for both local and systemic drug therapy. Traditional rectal dosage formulations have histori- cally been used for localised treatments, including laxatives, hemorrhoid therapy and antipyretics. However, this form of drug dosage often feels alien and uncomfortable to a patient, encouraging refusal. The limitations of conventional solid suppositories can be overcome by creating a thermosen- sitive liquid suppository. Unfortunately, there are currently only a few studies describing their use in therapy. However, recent trends indicate an increase in the development of this modern therapeutic system. This review introduces a novel rectal drug delivery system with the goal of summarising recent developments in thermosensitive liquid suppositories for analgesic, anticancer, antiemetic, antihypertensive, psychiatric, antiallergic, anaesthetic, antimalarial drugs and insulin. The report also presents the impact of various types of components and their concentration on the properties of this rectal dosage form. Further research into such formulations is certainly needed in order to meet Citation: Bialik, M.; Kuras, M.; the high demand for modern, efficient rectal gelling systems. Continued research and development Sobczak, M.; Oledzka, E.
    [Show full text]
  • Intranasal Drug Delivery - General Principles
    Intranasal drug delivery - General principles The nasal cavity's easily accessible, rich vascular plexus permits topically administered drugs to rapidly achieve effective blood levels while avoiding intravenous catheters. This is most effectively accomplished by distributing drug solutions as a mist rather than as larger droplets which may aggregate and run off instead of being absorbed. Because of this easily accessed vascular bed, nasal administration of medications is emerging as a promising method of delivering medications directly to the blood stream. This method of delivery can eliminate the need for intravenous catheters while still achieving rapid, effective blood levels of the medication administered. Administering medications via the nasal mucosa offers several advantages: 1. The rich vascular plexus of the nasal cavity provides a direct route into the blood stream for medications that easily cross mucous membranes. 2. This direct absorption into the blood stream avoids gastrointestinal destruction and hepatic first pass metabolism (destruction of drugs by liver enzymes) allowing more drug to be cost-effectively, rapidly, and predictably bioavailable than if it were administered orally. 3. For many IN medications the rates of absorption and plasma concentrations are comparable to intravenous administration, and are typically better than subcutaneous or intramuscular routes. 4. Ease, convenience and safety: IN drug administration is essentially painless, and does not require sterile technique, intravenous catheters or other invasive devices, and it is immediately and readily available for all patients. 5. Because the nasal mucosa is nearby the brain, cerebrospinal fluid (CSF) drug concentrations can exceed plasma concentrations. IN administration may rapidly achieve therapeutic brain and spinal cord (CNS) drug concentrations.
    [Show full text]
  • A Thesis Entitled Nose to Brain Delivery of Antiepileptic Drugs
    A Thesis entitled Nose to Brain Delivery of Antiepileptic Drugs Using Nanoemulsions by Salam Shanta Taher Al-Maliki Submitted to the Graduate Faculty as partial fulfillment of the requirements for the Master of Science Degree in Pharmaceutical Sciences, Industrial Pharmacy ________________________________________ Jerry Nesamony, Ph.D., Committee Chair ________________________________________ Sai Hanuman Sagar Boddu, PhD, Committee Member ________________________________________ Caren L. Steinmiller, PhD, Committee Member ________________________________________ Patricia R. Komuniecki, PhD, Dean College of Graduate Studies The University of Toledo December 2015 Copyright 2015, Salam Al-Maliki This document is copyrighted material. Under copyright law, no parts of this document may be reproduced without the expressed permission of the author. An Abstract of Nose to Brain Delivery of Antiepileptic Drugs Using Nanoemulsions by Salam Al-Maliki Submitted to the Graduate Faculty as partial fulfillment of the requirements for the Master of Science Degree in Pharmaceutical Sciences Industrial Pharmacy The University of Toledo December 2015 The objective of this research work was to formulate and develop an intranasal oil-in- water nanoemulsion (NE) using spontaneous emulsification method. Based on ternary phase diagram, emulsification time, and drug solubility study, the composition ratio of surfactant:co-surfactant:oil was optimized to 2:1:1. The model antiepileptic drug chosen for loading was phenytoin. The NE preparation was evaluated for particle size, zeta potential, electrical conductivity, pH, % transmittance, polarized light microscopy, in vitro drug release studies using HPLC, sterility validation, differential scanning calorimetry (DSC), and in vitro nasal toxicity testing in bovine nasal mucosa. The nanoemulsion formulations were then subjected to stability studies for six months by storing formulations at 25±5°C and 5±3°C.
    [Show full text]
  • FDA-Approved Medications for Smoking Cessation
    PHARMACOLOGIC PRODUCT GUIDE: FDA-Approved Medications for Smoking Cessation NICOTINE REPLACEMENT THERAPY (NRT) FORMULATIONS BUPROPION SR VARENICLINE GUM LOZENGE TRANSDERMAL PATCH NASAL SPRAY ORAL INHALER Nicorette1, Generic Nicorette1, Generic NicoDerm CQ1, Generic Nicotrol NS2 Nicotrol Inhaler2 Zyban1, Generic Chantix2 OTC Nicorette1 Mini OTC (NicoDerm CQ, generic) Rx Rx Rx Rx PRODUCT 2 mg, 4 mg OTC 7 mg, 14 mg, 21 mg (24-hr release) Metered spray 10 mg cartridge 150 mg sustained-release tablet 0.5 mg, 1 mg tablet original, cinnamon, fruit, mint 2 mg, 4 mg; cherry, mint 10 mg/mL nicotine solution delivers 4 mg inhaled vapor • Recent (≤ 2 weeks) myocardial • Recent (≤ 2 weeks) myocardial • Recent (≤ 2 weeks) myocardial • Recent (≤ 2 weeks) myocardial • Recent (≤ 2 weeks) myocardial • Concomitant therapy with medications/ • Severe renal impairment (dosage infarction infarction infarction infarction infarction conditions known to lower the seizure adjustment is necessary) • Serious underlying arrhythmias • Serious underlying arrhythmias • Serious underlying arrhythmias • Serious underlying arrhythmias • Serious underlying arrhythmias threshold • Pregnancy3 • Serious or worsening angina • Serious or worsening angina • Serious or worsening angina • Serious or worsening angina • Serious or worsening angina • Hepatic impairment and breastfeeding pectoris pectoris pectoris pectoris pectoris • Pregnancy3 and breastfeeding • Adolescents (<18 years) • Temporomandibular joint disease • Pregnancy3 and breastfeeding • Pregnancy3 and breastfeeding •
    [Show full text]
  • Naloxone Products and Their Pricing in Medicaid, 2010–18
    HEALTH POLICY CENTER RESEARCH REPORT Naloxone Products and Their Pricing in Medicaid, 2010—18 Trends for Opioid Overdose Reversal Drugs Lisa Clemans-Cope Marni Epstein Emma Winiski August 2020 ABOUT THE URBAN INSTITUTE The nonprofit Urban Institute is a leading research organization dedicated to developing evidence-based insights that improve people’s lives and strengthen communities. For 50 years, Urban has been the trusted source for rigorous analysis of complex social and economic issues; strategic advice to policymakers, philanthropists, and practitioners; and new, promising ideas that expand opportunities for all. Our work inspires effective decisions that advance fairness and enhance the well-being of people and places. Copyright © August 2020. Urban Institute. Permission is granted for reproduction of this file, with attribution to the Urban Institute. Cover image by Tim Meko. Contents Acknowledgments iv Executive Summary v Naloxone Products and Their Pricing in Medicaid, 2010–18 1 Data and Methods 5 Estimation of Federal Rebates 6 Key Measures 7 Findings 8 Annual Naloxone Prescriptions in Medicaid 8 Market Shares of Medicaid-Covered Prescriptions for the Most Common Naloxone Products 9 Annual Rebate-Adjusted Medicaid Spending on Naloxone 11 Rebate-Adjusted Medicaid Spending per Naloxone Prescription 13 Recent State Variation in Rebate-Adjusted Medicaid Spending per Naloxone Prescription by Product Type 15 Discussion 19 Conclusion 20 Limitations 21 Appendix. Quarterly Prescriptions for and Rebate-Adjusted Spending on Naloxone in Medicaid, 2010–18 22 Prescriptions 22 Rebate-Adjusted Spending 23 Notes 24 References 26 About the Authors 31 Statement of Independence 32 Acknowledgments This report was funded by the Laura and John Arnold Foundation.
    [Show full text]