Pharmagesic is an innovative transdermal system that uses PharmaDur polymer technology to form an invisible hydrogel film on the skin, providing sustained release of active ingredients for up to 24 hours with a single application. This summary technology enables higher drug dosages to be delivered transdermally compared to traditional patches and gels. Pharmagesic products in development include a transdermal gel for systemic delivery of diclofenac and a topical gel for local delivery to sites of pain.

1. PHARMAGESIC™
TRANSDERMAL SYSTEM
An Innovative Approach to Pain Management
P.O. Box 622, Swiftwater, PA 18370
United States
Tel: +1.570.460.1804
jay@ambianceventures.com
www.pharmadur.com
AmbianceVentures USA
Representing Polytherapeutics, Inc.

2. PHARMAGESIC OUTLINE
• PharmaDur polymer description.
• Performance attributes of PharmaDur in dermal
products.
• Pharmagesic™ Transdermal System.
- LOCAL & SYSTEMIC
• Intellectual Property
• Brief introduction to Polytherapeutics.

3. PHARMADUR®
POLYMER STRUCTURE
Water Soluble Polymer Chain
Water Insoluble
Styrenic Polymer Segments
HYDROPHILIC/HYDROPHOBIC
GRAFT COPOLYMER
COOH COOH
COOH COOH

4. PHARMADUR
“VIRTUAL PATCH”
• Dosage Form: PharmaDur polymer can be formulated
into conventional gels, creams and ointments.
• When the formultion is applied to skin, it forms an
invisible and imperceptible bioadhesive hydrogel film
(“virtual patch”).
• The formed film is retained on skin for 24 hours or
until it is washed away.

5. SCHEMATIC DIAGRAM OF
PHARMADUR VIRTUAL PATCH
Kishore Shah, Tracey Vlahovic, and Otto Mills, Poster - New Long Acting Topically Applied
Treatments, American Academy of Dermatology Annual Meeting (2007).

6. B. Michniak-Kohn, K. Shah, B. Kilfoyle, and O. Mills, Poster – Linking
Biophysical & Biochemical Findings with Clinical Use, American Academy
of Dermatology Annual Meeting (2008).
PharmaDur Film
Stratum Corneum
Epidermis
FLUORESCENCE MICROSCOPIC EXAMINTION OF
PHARMADUR FILM ON SKIN

7. PHARMADUR™
RETENTION ON SKIN
• Fluorescent PharmaDur™ solution in ethanol
was painted (X) on hands of a human subject.
Examination of the painted surface initially and
24 hours later, under illumination with UV light,
showed clearly visible ‘X’.
(AMA Laboratories, New City, NY)
• Assessment by touching site of application with
moist finger indicates slippery feel for 24+ hours.

8. PharmaDur®
Dermal Formulations
PERFORMANCE ATTRIBUTES
• Retains active @ the site of application & provides
sustained release of active agent for 24 hours.
• Significantly increases the efficacy of penetration enhancer
in skin permeation of actives.
• Prevents transfer of active to fingers, clothing, towels, and
bed linen.
• Improves bioavailability & effectiveness of the active.
“STRONGER & LONGER”
“PharmaDur®
Bioadhesive Delivery System”, K. R. Shah in John J. Wille, ed.
“Skin Delivery Systems; Transdermals, Dermatologicals, and Cosmetic Actives”,
Blackwell Publishing, Ames, Iowa, © 2006, p 211-222.

9. KEY ADVANTAGES OF
PHARMADUR VIRTUAL PATCH
• Enables delivery of higher dosage of drug
or drug having low skin permeability. (Up
to 100 to 150 mg /day systemic dose)
• Sustained Therapeutic Effectiveness For 24
hours.
• Flexibility of dosing.
• Avoids GI tract.
• Bypasses hepatic first pass metabolism.
• Ease of manufacture.

10. PHARMAGESIC™
TRANSDERMAL SYSTEM
TWO PRODUCTS
1. Provide transdermal delivery of diclofenac
for systemic activity. Produce sustained
effective drug concentrations in blood.
Once/Day or bid. (SYSTEMIC)
2. Topical delivery of diclofenac for site
specific efficacy. (LOCAL)
Once/Day

11. PHARMAGSIC
SKIN PERMEATION STUDY
• Solution (50 µl) of the gel placed on surface of
human cadaver skin mounted in Franz cell.
• Donor compartment kept open to allow the solution
to dry out on skin.
• Receptor phase: phosphate buffer @ pH 7.4 and a
temperature of 37° C.
• CONTROL: Voltaren®
Gel (Novartis)
• Aliquots of the receptor phase analyzed by HPLC
for diclofenac at different time intervals.

12. DICLOFENAC J
FOR SELECTED FORMUALTIONS
Normalized wrt to Voltaren Gel = 1.16 mcg/sq. cm. hr
0
2
4
6
8
10
12
14
16
18
1 2 3 4 5 6 7 8 9
Formulation Number
DiclofenacJ,mcg/sqcm.hr

13. DICLOFENAC J, mcg/sq. cm. hr
Subject to Subject Variations
Cadaver Donor
Number
Voltaren Gel Pharmagesic SYSTEMIC
Normalized wrt Voltaren Gel
1 0.6
2 1.2
3 1.6 10.5
4 0.4
5 0.5
6 2 9
7 1.3 12.5
8 1.2 10.7
9 0.5 16.7
10 2.3 12.4
AVERAGE 1.16 12

14. DICLOFENAC, J
-50
0
50
100
150
200
250
300
350
400
0 5 10 15 20 25 30 35
Time, hours
CumulativeAmtofDiclofenac,
mcg/sq.cm
Pharmagesic SYSTEMIC
Voltaren Gel
B. Michniak-Kohn , D. Kaushik, and K. Shah, unpublished results (2010)

15. PHARMAGESIC™ LOCAL
PRODUCT DESCRIPTION
Dosage Form: Medium viscosity clear
hydroalcoholic gel/solution.
API: Diclofenac sodium.
Ingredients: USP and/or FDA approved
pharmaceutical excipients &
PharmaDur®
polymer.
Application:~ 700 mg Gel Once/day over affected
area (e.g. knee, wrist, tendon, etc.).
When applied to skin, it dries to form an invisible
PharmaDur®
hydrogel film (Virtual Patch) containing
the drug and the excipients.

16. PHARMAGESIC LOCAL
VS VOLTAREN GEL
Performance
Property
Voltaren®
Gel Pharmagesic
LOCAL
Efficacy Effective J = ~ 3 x
Voltaren Gel
Dosage 2-4 grams/knee 700 mg/knee
Dosing
Frequency
4 times/day Once/day
Drying Time ~ 10 minutes ~ 5-7 minutes

17. PHARMAGESIC
INTELLECTUAL PROPERTY
• U.S. Patent 5,942,243
Mucoadhesive compositions for administration of
biologically active agents to animal tissue.
• EP 1 077 678 B1
Mucoadhesive compositions for administration of
biologically active agents to animal tissue.
• Composition for transdermal administration of non-
steroidal anti-inflammatory agent
- U.S. Patent Pending.
- PCT International Pending.

18. PHARMAGESIC SUMMARY
• Pharmagesic LOCAL offers significant
performance enhancement over competitive
products (Voltaren & Pennsaid).
Greater effectiveness with once/day dosing
vs 4 times /day dosing
• Less product application per dose.
~ 700 mg per dose Vs 2 or 4 g per dose
• Internationally patent protected technology.
• Available marketing exclusivity.

19. THE PHARMADUR EFFECT
• PharmaDur polymer exerts a profound effect on
enhancement of the penetration rate of a drug
through skin. Skin permeation enhancer by itself
is not the sole determining factor.
e.g Diclofenac JPharmagesicSYSTEMIC/JPennsaid = ~ 50
NOTE: Pennsaid®
Solution contains 45% DMSO, a
powerful skin penetration enhancer.
• Combination of the Virtual Patch & the rate
enhancement effect enables transdermal drug
delivery dosages up to 100-150 mg of /day.

20. SCOPE OF TRANSDERMAL
DRUG DELIVERY
ALL DRUGS
Currently
Feasible for
Transdermal
Delivery
Feasible with
PharmaDur®
Virtual Patch
Technology

21. POLYTHERAPEUTICS
MISSION
• Research & Development
Polymer Technologies & Products for
Pharmaceutical & other Healthcare Uses
• License Products to other Corporations for
World Wide Marketing
• Manufacture PTI Developed Products for
Corporate Licensees where applicable.

22. POLYTHERAPEUTICS, INC.
• Research & Development laboratory in New
Brunswick Technology Center, New Brunswick, NJ.
• PharmaDur™ delivery system is commercially
utilized in two Rx dermatological products and more
than 15 cosmetic products by licensees of
Polytherapeutics. (e.g. Umecta®
PD & Aclaro®
PD, JSJ
Pharmaceuticals; High Definition Healthy FX Foundation, Smashbox
Cosmetics – Estee Lauder, Murad Cosmetics)
• Collaboration with a big pharma company
in ophthalmic drug delivery.
www.pharmadur.com

23. PharmaGesic™
Performance
Enhancement
Product
Differentiation
Marketing
Edge
AmbianceVentures USA – Global Marketing Partners
Jay@Ambiance-Ventures.com
Global licensinG oPPortunity