suitable polymer suitable drug

Dr. Mohamed Ghobashy (P.hD.)B.SC 1999M.SC 2007P.hD. 2013

Radiation Research of Polymer DepartmentNanotechnology and Hydrogel lab.

National Center for Radiation Research and Technology (NCRRT) Atomic Energy Authority

NCRRTAEAE

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Giulio Natta (Nobel prize 1963)

Cellulose acetate

2

Charles Goodyear1800-1860Thomas Hancock

(1786-1865)

Hist

ory

of p

olym

ers

Hist

ory

of p

olym

ers

Hist

ory

of p

olym

ers

Hist

ory

of p

olym

ers

Hist

ory

of p

olym

ers

Hist

ory

of p

olym

ers

Hist

ory

of p

olym

ers

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Wallace Hume CarothersPolyamides 6,61896

1938 1937 

Wallace Hume CarothersPolyamides 6,6

1896 1938  1937 

NO RUN (NURON) NILLON NYLON

Polyamides 6,6

Wilmington (Delaware)

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HOW

LON

G DOES IT TAKE?

POLYMERIC MATERIAL DEGRADATION TIMECotton rags 1-5 months

Paper 2-5 months

Rope 3-14 months

Orange peels 6 months

Wool socks 1 to 5 years

Cigarette butts 1 to 12 years

Plastic coated paper milk cartons 5 years

Plastic bags 10 to 20 years

Nylon fabric 30 to 40 years

Aluminum cans 80 to 100 years

Plastic 6-pack holder rings 450 years

Glass bottles 1 million years

Plastic bottles May be never 505/02/20235/38

Problem Description 1

6

• In recent years, there is increased number of active

pharmaceutical ingredients with high therapeutic

activity, but very low water solubility. Thus, a great

challenge for pharmaceutical technology is to

manufacture successful formulations and efficient drug

delivery systems to overcome these dissolution

problems. In case of poorly water soluble drugs,

dissolution is the rate limiting step in the process of

drug absorption. So, bioavailability problems are

associated with extremely hydrophobic drugs (aqueous

solubility < 0.1 mg / ml at 370C)

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Problem Description 2

7 Drug levels in the blood with (a) traditional drug dosing and (b) controlled-delivery dosing

SUB-ACUTE TOXICITY-

• Identify target organs susceptible to drugs toxicity

• Three doses are used on two animal species

• Animals maintained at the max. tolerated doses for a minimum period of 4 weeks to a max. period of 3 months

• Finally ,the animals are killed and subjected to histopathological examination.

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Polymer chose

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Same shape

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Polypeptide nanowire:In a manner, amino acids combinetogether in chain by formation ofpeptide bond.

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DNA double nanowire:Basic building block ofDNA is nucleotide, it isa five member ringdeoxyribose withphosphate group, anucleic acid base R.

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Types of polymer

Neutral Basic Acidic

Amphiphilic 1205/02/202312/38

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Crystanility of polymer

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Crystanility of polymer

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Wurster processing (1949)• The Wurstur process is essentially a coating process

applied after a drug core is formed.• The polymer shell is applied via spraying while the drug

cores (liquid or solid) is suspended and recirculated in a gas stream

Gas

DrugPolymer Drug

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Electrospinning Process

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Surface erosion(e.g., polyanhydrides)

– When the polymer is exposed to water hydrolysis occurs– Hydrolysis degrades the large polymers into smaller biocompatible compounds– These small compound diffuse from the interface of the polymer– Loss of the small compounds reveals drug trapped within– Note these polymer do not swell.

Addwater

Addtime

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Drug release by diffusion• Early encapsulation and entrapment systems released the drug from within the polymer via molecular

diffusion– When the polymer absorbs water it swells in size– Swelling created voids throughout the interior polymer– Smaller molecule drugs can escape via the voids at a known rate controlled by molecular

diffusion (a function of temperature and drug size)

Addwater

Addtime

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Stimuli Responsive

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EUDRAGIT® Acrylic Drug Delivery Polymerspoly(meth)acrylates for pharmaceutical applications, which are known worldwide in the industry under the trade name

EUDRAGIT.®

UDRAGIT® S 100

methacrylic acic and methyl methacrylate.

EUDRAGIT® E 100 dimethylaminoethyl methacrylate, butyl

methacrylate, and methyl methacrylate 2223/38

No drug–polymer interactions were reportedwhen examined using FTIR

The anionic polymer protected the drug by preventing its gelling and clumping in situ, while the nonionic polymer promoted gelling

Fan et al. (2009)Fan C, Pai-Thakur R, Phuapradit W, Zhang L, Tian H, Malick W, Shah N, Kislalioglu MS (2009) Impact of polymers on dissolution performance of an amorphous gelleable drug from surfacecoated beads. Eur J Pharm Sci 37(1):1–10

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Crushed API beadlets in the pH 7.4 phosphate buffer solution, (a) Eudragit® L100beadlets with exposed cores and (b) PVP® K30 beadlets exhibiting the characteristic gelling of the amorphous API

No drug–polymer interactions were reported when examined using FTIR, implying that this factor did not play a role in the differences observed in the release profiles. The anionic polymer protected the drug by preventing its gelling and clumping in situ, while the nonionic polymer promoted gelling (Fig). On the other hand, gelling, clumping, and agglomeration were observed on the surface of the particles coated with PVP K30 which resulted in slow and incomplete release of the drug. From the anionic polymer coating, greater than 90% drug was dissolved in 50 min, whereas the nonionic polymer coating released 60% drug in 5 h (Fig.)

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Fan et al. (2009)Fan C, Pai-Thakur R, Phuapradit W, Zhang L, Tian H, Malick W, Shah N, Kislalioglu MS (2009) Impact of polymers on dissolution performance of an amorphous gelleable drug from surfacecoated beads. Eur J Pharm Sci 37(1):1–10

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Fan et al. (2009)Fan C, Pai-Thakur R, Phuapradit W, Zhang L, Tian H, Malick W, Shah N, Kislalioglu MS (2009) Impact of polymers on dissolution performance of an amorphous gelleable drug from surfacecoated beads. Eur J Pharm Sci 37(1):1–10

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Shah et al. 2012)Shah N, Sandhu H, Phuapradit W, Pinal R, Iyer R, Albano A, Chatterji A, Anand S, Choi DS, Tang K, Tian H, Chokshi H, Singhal D, Malick W (2012) Development of novel microprecipitated bulk powder technology for manufacturing stable amorphous formulations of poorly soluble drugs. Int J Pharm 438:53–60

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Jennifer Dressman is Professor of Pharmaceutical 

Prof. Dr. Jennifer B. DressmanInstitute of Pharmaceutical Technology

BiocenterJohann Wolfgang Goethe University

Max-von-Laue-Str.. 960438 Frankfurt am Main, GERMANY

. - .dressman@em uni frankfurt de

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vitro study

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self-emulsification

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Schematic diagramof a multiple-step in vitro digestion model to simulate the whole of the GI tract.

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My Studies On Drug Release

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05/02/202332(1) Coil (2) Water Inlet (3) Water Outlet (4) Sample (5) Closed Test Tube (6) Water Madium

Apparatuses to Study The Effect of Magnetic Field on Drug Release

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Time(min.)0 20 40 60 80 100 120

Dru

g R

elas

e (m

g)

0.00

0.05

0.10

0.15

0.20

0.25

0.30

0.35

Drug release amount from Fe3O4/PAAc/PVA loaded with theophylline drug (○) no magnetic field (●) magnetic field34/38

Drug Release Measurement E.F.

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(1 )Two Carbon Electrodes (2) Spring Wire (3) Gel Spice

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Electro-controlled release of theophylline from AMPS/AAc hydrogel by switching the applied electric field on and off.36/38

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Liner relation between the amount of loss water by deswelling and the amount of drug release under effect of 1 DC volt in water medium for (75-25)AAc-AMPS 36/38

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