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january 2011

Exciting developments are occurring in the field of alternative drug delivery—a phrase that describes the reformulation of drugs to enable lower doses, more convenient delivery routes, and supplemental therapeutic indications. This report presents an overview of these developments, describes the options that new formulation technologies are creating, and explores the medical and commercial perspectives.

Discussed in this report: • The enabling role of medical devices in drug delivery technology

• Drug delivery applications of nanotechnology

• How advanced drug delivery can overcome biological barriers

• alternative delivery modalities for biotechnology-derived drugs

• nucleic acid delivery technologies

• resurgence of transdermal delivery technology

• role of alternative delivery in drug lifecycle management

• Corporate showcase of 29 drug delivery companies including nanoViricides, Starpharma Holdings, CyDex Pharmaceuticals, nektar Therapeutics, SurModics, MannKind, nanoBio, and Vyteris

Advanced Drug Delivery TechnologiesEnabling Drug reformulations and administration routes Author: Hermann AM Mucke, PhD

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oVErVIEw

Advanced Drug Delivery Technologies:Enabling Drug reformulations and administration routes

Author: Hermann AM Mucke, PhD

The pharmaceutical industry is paying attention to aspects of innovation and business development that it has always employed occasionally but not systematically. These involve finding new uses for known active ingredients, by repurposing them to entirely new therapeutic fields or by leveraging modern formulation technology to significantly improve their properties.

We begin by describing the main routes of drug delivery (oral, injection/infusion, and transdermal), their pros and cons, and the environment in which they are deployed. We also explain that “alternative” drug delivery is not so much about fundamentally different “roads into the unknown” that have not been taken before, but about new dimensions of the known routes. In other words, what we call alternative drug delivery consists of clever technical advancements along what ultimately are the known routes.

The enabling role of medical devices in drug delivery technology is addressed next. Drug-eluting stents and other implantable drug delivery devices are presented, as well as externally applied devices. Next, drug delivery applications of nanotechnology are introduced. When combined with appropriate targeting moieties, drug-coated nanoparticles, drug-encapsulating liposomes and nanotubes, and tree-like dendrimers enable organ and tissue targeting.

After a discussion of ways in which drug delivery can overcome anatomical and functional barriers, the report turns to alternative delivery modalities for peptides, proteins, and antibodies. These biotechnology-derived drugs were formerly administered by injection alone, but today, solutions for inhaled, transdermal, and even oral delivery are available or under investigation for most established products.

Next we consider nucleic acid delivery technologies, which are not actually “alternative” but are initially enabling for their novel cargoes, since unprotected or untargeted delivery of gene therapies or RNAi is inconceivable. We then move on to developments in transdermal delivery technology, which includes active systems where delivery is driven by microneedles or energy applied via ultrasound or lasers.

We then explore the role of alternative delivery in drug lifecycle management. Case studies demonstrate how cleverly applied technologies can reinvigorate drugs that have lost patent protection or have not fully exploited their potential. We also present unique technologies with broad applicability in alternative drug delivery. Regulatory pathways and timelines for obtaining patents for the new products are addressed.

Selected drug delivery firms, their technological approaches, pipelines, and collaborations are profiled. We conclude with an outlook to what we call the “Preprogrammed Rise of Alternative Drug Delivery”—an unavoidable development driven by the fact that lifecycle management and recouping of value from existing resources will continue to rule the pharmaceutical industry’s business throughout the 2010s.

To order a report, e-mail rlaraia@healthtech.com, call Rose LaRaia at 781-972-5444, or order on-line at InsightPharmaReports.com/DrugDelivery

FIgurES anD TaBlESFigure 1.1. Enhancement of Drug Prop-erties vs. Enablement of New Routes and Therapies through Formulation Technology

Figure 2.1. Duros System

Figure 3.1. Computed Surface-Mass Values for Spheres and Cubes on the Micrometer to Nanometer Scale

Figure 3.2. Schematic of a Simple Liposome

Figure 3.3. Schematic of a Dendrimer and a Dendron

Figure 3.4. Schematic Representation of C60 Fullerene

Figure 6.1. Schematic of Ablitech’s Versadel Technology

Figure 7.1. Microneedle-Assisted Trans-dermal Drug Delivery System

Table 8.1. Drug Delivery-Enabled Prod-uct Clinical Development & Approval Times & Success Rates

About The AuthorHermann AM Mucke, PhD, spent 17 years in academia and industry before he founded H.M. Pharma Consultancy (www.hmpharmacon.com) in 2000 to become an independent pharmaceutical consultant, analyst, and science author. His last industry position was Vice President R&D in a European pharmaceutical company, which he helped to take public on the Frankfurt Stock Exchange in 1999. Since then, Dr. Mucke, who holds a PhD in biochemistry from the University of Vienna (Austria), has become a consultant and advisory board member for several European and American pharmaceutical companies and a regular reviewer of drugs and patents for Thomson Current Drugs and Ashley Publications. Dr. Mucke is based in Vienna.

New Interactive Report Format Now Available!The Electronic version of the reports is now more robust, interactive documents offering the following enhancements: 

• anchored navigation bars on each page with links to the table of contents, a search feature, and previous/next/return page arrows.

• Fully hyperlinked table of contents to navigate you directly to specific content, tables and figures.

• Tables and figures found within each report are available for download in jPEg or PDF format.

• Hyperlinks to navigate you to organization and company sites, referenced reports, and a wealth of external information.

• Dynamic references viewable via pop-ups in direct proximity to the referenced content.

• Horizontal formatting, font usage and type size have all been optimized for better screen display.

• we also continue to provide a full list of references at the conclusion of each report.

To order a report, e-mail rlaraia@healthtech.com, call Rose LaRaia at 781-972-5444, or order on-line at InsightPharmaReports.com/DrugDelivery InsIght Pharma rePorts 250 First Avenue • Suite 300 • Needham, MA 02494 • 781-972-5444 • InsightPharmareports.com/DrugDeliveryA division of Cambridge Healthtech Institute

TaBlE oF ConTEnTS

ChAPTER 1CLASSiCAL RoUTES oF DRUg DELiVERy: THEiR LiMiTATionS AnD THE ALTERnATiVES

1.1. The Oral Route: Obvious But Limited in Non-Obvious Ways

1.2. The Parenteral Routes

1.3. Systemic Topical Delivery

1.4. What Is “Alternative” Drug Delivery?

ChAPTER 2THE MARRiAgE oF DRUgS AnD DEViCES: REinVigoRATing oLD TECHnoLogiES

2.1. Drug-Eluting Stents

2.2. Metered-Dose Inhalers

2.3. Programmable and Self-Programming Devices

pumps and “clever pills”

2.4. Externally Triggered Release from Liposomes

2.5. Long-Acting Depots with Biodegradable Polymers

2.6. Advances in Injection Technology needleless injectors

autoinjectors: from battlefield to living room

2.7. New Approaches to Transdermal and Transmucosal Delivery medicated clothing

ChAPTER 3nAnoSCALE DRUg VEHiCLES: REDEFining DRUg DELiVERy TECHnoLogy

3.1. Two Types of Nanomedicine

3.2. Specific Characteristics of Nanoparticulates interaction with biological fluids

3.3. Improving Resorption and Organ System Barrier Penetration

3.4. Colloids: The Natural State of Nanoscale Systems in Biology

3.5. Dendrimers: Uniquely Designed Multifunctional Nanoglobules

3.6. Quantum Dots: A Very Special Type of Nanoparticle

3.7. Spherical Cages and hollow Fibers

3.8. Potential Medical Safety Issues with Nanostructures

ChAPTER 4ADVAnCED oRgAn AnD TiSSUE TARgETing

4.1. Controlled Barrier-Penetration Technologies

4.2. Engaging Blood-Brain Barrier Transporters

4.3. Solid Tumors implant-based approaches are of limited utility

a universe of advanced tumor delivery formulations

the resurgence of gold in cancer therapy

4.4. Intraocular Implants and Related Delivery Systems

4.5. Localized Drug Delivery in Oral health

4.6. Fiber Technology for Surgical Drug Delivery Implants

4.7. Protection and healing of Blood Vessels

4.8. Summary

ChAPTER 5THE CHALLEngE oF PEPTiDES AnD PRoTEinS

5.1. Oral Bioavailability of Proteins: The “holy Grail” Attained (To a Degree)

5.2. The Interplay Between Immunogenicity and Formulation

5.3. Attempts and Solutions for Insulins inhaled insulin oral insulin

5.4. Needle-Free Vaccination oral vaccines

transdermal and transmucosal vaccines

influenza, hiv, and hepatitis c

5.5. Pernasal and Oral Calcitonin

ChAPTER 6TECHnoLogiES FoR nUCLEiC ACiD DELiVERy

6.1. A New Paradigm Requires New Modalities of Delivery

6.2. Restorative Gene Therapies

6.3. RNA Interference Therapeutics

ChAPTER 7TRAnSDERMAL AnD TRAnSMUCoSAL PRESEn-TATionS: SELECTED TREnDS

7.1. Recent Innovations in Transdermal Delivery Systems case study: transdermal presentations for alzheimer drugs

7.2. Vaginal Drug Delivery: An Emerging Field

ChAPTER 8ADVAnCED DRUg DELiVERy AnD THE PRoDUCT LiFECyCLE

8.1. Alternative Drug Delivery: Salvaging and Extend-ing Market Share case study #1: aripiprazole, an antipsychotic in many forms

case study #2: staccato loxapine, an antipsychotic made inhalable

case study #3: halozyme, a subcutaneous delivery technology for biotech drugs

case study #4: elan drug technologies, a universal for- mulation tool provider

8.2. Patenting Alternative Delivery Methods: Walking a Narrow Line

8.3. Regulatory Challenges and Opportunities the us process

the european process

no “smooth sailing” guaranteed for reformulated drugs

ChAPTER 9CoMPAny AnD PiPELinE PRoFiLES

9.1. Companies with Various Focus Areas access pharmaceuticals

capsulution pharma catalent pharma solutions

celator pharmaceuticals, inc. celator pharmaceuticals corp. chimerix

selecta biosciences

nanoviricides

starpharma holdings cydex pharmaceuticals

emisphere technologies

merrion pharmaceuticals, ltd. merrion pharmaceuticals, llc

nektar therapeutics

polytherics oramed

innocoll technologies surmodics

calando pharmaceuticals

9.2. Companies with a Focus on Inhalation mannkind map pharmaceuticals

akela pharma microdose therapeutx

optinose

9.3. Companies with a Focus on Transdermal Delivery altea therapeutics dharma therapeutics

intercell zogenix nanobio vyteris

makefield therapeutics

ChAPTER 10SUMMARy AnD PERSPECTiVES

10.1. The Breathtaking Development of Drug Delivery

10.2. New Formulations: Twice as Lucrative as New Drugs

10.3. Lifecycle Management Rules the Strategy

10.4. The “Preprogrammed” Rise of Alternative Drug Delivery

10.5. International Cooperation Is Called For

10.6. The Role of Intellectual Property in Alternative Drug Delivery

10.7. Summary

REFEREnCES

CoMPAny inDEx wiTH wEb ADDRESSES

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reLateD rePortrnai therapeutics: second-generation Candidates Build momentumMany established pharma companies have entered into major deals with some of these RNAi therapeutics companies. These have attracted the interest of the investment community and the pharmaceutical industry.this report covers:

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