cyclodextrins ashwani goyal

8/9/2019 Cyclodextrins Ashwani Goyal

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PRESENTATIONPRESENTATION

ONON

CYCL DEXTRINSCYCL DEXTRINS

AS EXCIPIENTSAS EXCIPIENTS

PRESENTED BY: ASHWANI GOYALPRESENTED BY: ASHWANI GOYAL

M.PHARMACY 1M.PHARMACY 1STST SEMESTERSEMESTER

DEPARTMENT OF PHARMACEUTICSDEPARTMENT OF PHARMACEUTICS

CHITKARA SCHOOL PHARMACYCHITKARA SCHOOL PHARMACY


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INTRODUCTION

EXCIPIENTS1.WHAT ARE EXCIPIENTS?

2.WHY WE USE EXCIPIENTS?

3.WHAT TYPE OF EXCIPIENTS ARE UPHARMACEUTICALS?

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EXCIPIENTS

EXCIPIENTS

An excipient is an inactive substance used as a carrier

for the active ingredients of a medication.

In many cases, an "active" substance (suchas aspirin) may not be easily administered

and absorbed by the human body

Example: Binders,Disintegrants, Diluents,Flavours,Cyclodextrins.

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TYPES OF EXCIPIENTS

Antiadherents

USED to reduce

the adhesion between

the powder (granules)

Binders

Binders hold the

ingredients in a tablet

together

Coatings

tablet ingredients from

deterioration by moisture

Disintegrants

dissolve when wet

causing the tablet to break

apart

F

fill

Flavours

used to mask unpleasant

tasting active ingredients

Colours improve the

appearance of a

formulation

Glidants

promote powder flow by

reducing interparticle

friction

Lubricants

Prevent ingredients from

clumping together and

from sticking to the tablet

punches

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CYCL DEXTRINS

1.WHAT ARE CYCLODEXTRINS? 2.HOW THEY ARE DISCOVERED?

3.WHAT IS THE PRESENT STATUS OF

4.HOW THEY ARE PRODUCED? 5.WHAT IS THE USE OF CDs IN

PHARMACEUTICALS?

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CYCL DEXTRINS

DEFINATION:

CDs are cyclic oligosaccharides derived fro

starch containing six (CD), seven (CD), (CD), nine (CD), ten (CD) or more (-1

linked -D-glucopyranose units.

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HISTORYIn 1891 a French scientist, A. Villiers,

described a bacterial digest that he hadisolated from starch.

results indicated that the substancewas a dextrin

Later Franz Schardinger, described two

crystalline compounds -dextrin and -dextrinSchardinger identified -dextrin as

Villiers' cellulosine

Now these compounds are commonlycalled cyclodextrins

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TYPES OF CDs

CDs

NATURAL SYNTHETIC

-, -, and -CDsSulfobutylether--CD Methyl--CD

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COMMERCIAL AVAILABILITY

The world's first CD-containing pharmaceutical product,prostaglandin E2/CD (Prostarmon Esublingual tablets),

was marketed in Japan in 1976.

Twelve years later, the first European CD-basedpharmaceutical product, piroxicam/CD (Brexin tablets),was marketed and in 1997, the first US-approved product

Worldwide, 35 different drugs are currently marketed as

solid or solution-based CD complex formulationsIn these pharmaceutical products, CDs are mainly used ascomplexing agents to increase the aqueous solubility of

poorly water-soluble drugs, to increase their bioavailabilityand stability

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SOME MARKETED CD BASED


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SOME MARKETED CDs BASED

PCEUTICALS.

Drug/cyclodextrin Trade name Formulation Comp

Alpha Cyclodextrin

Alprostadil Caverject Dual i.v. solution Pfizer (E

Cefotiam-hexetil HCl Pansporin T Tablet Takeda

-Cyclodextrin (CD)

Nimesulide Nimedex Tablets Novartis (

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STRUCTURE AND PRODUCTIO


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STRUCTURE AND PRODUCTIO

OF CDs.

Due to the chair

conformation of the

glucopyranose units, the

CDs take the shape of atruncated cone or torus

rather than a perfect

cylinder.

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STRUCTURE

Seco

-cyclodextrin- 7 sugar molecules -cyclo-dextrin- 6 sugar molecules -cyclodextrin- 5 sugar molecules

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PRODUCTION

Bacillus CirculanThe source of cyclodextrins

Treatment of starches with amylase from B. maceragives a crude mixture of CD (60%), CD (20%) CD (20%) together with small amounts of CDs w

more that 8 glucopyranose units.In reaction vats at pH 6.0-7.0 at 35-40 C.

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TOXOLOGICAL


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TOXOLOGICAL

CONSIDERATIONS

CONSIDEREDSAFE

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REGULATORY


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REGULATORY

STATUS

CD is listed in a number of pharmacopoeia

sources including the US

Pharmacopoeia/National Formulary

(USP/NF), European Pharmacopoeia

(Ph.Eur.) and Japanese Pharmaceutical

Codex (JPC). CD is similarly listed in thePh.Eur., USP/NF and JPC and CD is

referenced in the JPC and will soon be

included in the Ph.Eur

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ROLE OF CDs


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ROLE OF CDs

IN PCEUTICALS

CYCLODEXTRINS EFFECT THE FOLLPROPERTIES

1.Effect on

Drug Solubility and DissolutionPlaying a very important role in formulation of poorly water-soluble drugs by improving apparent dru

dissolution through inclusion complexation or solid dispersion, by acting as hydrophilic c

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Examples of CD enhanced


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Examples of CD-enhanced

Solubility and DissolutionCYCLODEXTRIN DRUGS

-CD Nimesulide,Sulfomethiazole,Lorazepam, Ketoprofen,Griseofulvin, Praziquantel,Chlorthalidone, Etodolac,Piroxicam,, Itraconazole,Ibuprofen

-CD Praziquantel

-CD Praziquantel, Omeprazole,DigoxinHP--CD Albendazole, DY9760e,

ETH615, LevemopamilHCl, Sulfomethiazole,Ketoprofen,, Griseofulvin,Itraconazole,Carbamazepine Zolpidem,Phenytoin, Rutin

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EFFECT ON DRUG


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EFFECT ON DRUG

BIOAVAILABILITY

CDs enhance the bioavailability of insoluble drugs by increasing the drug solubility, dissolution, and/or dru

increase the permeability of insoluble, hydrophobic drugs by making the drug available at the surface of

e.g, skin, mucosa, or the eye cornea, from where it partitions into the membrane without disrupting the lip

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EFFECT ON


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EFFECT ON

DRUG SAFETY CDs have been used to ameliorate the irritation caused by drugs. The increased drug eff

(i.e, reduction of the dose required for optimum therapeutic activity), caused by CD-solubility, may reduce drug toxicity by making the drug effective at lower d

The toxicities associated with crystallization of poorly water-solubparenteral formulations can often be reduced by formation of solub

complexes.

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EFFECT ON


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EFFECT ON

DRUG STABILITY CDs can improve the stability of several labile drugs against dehydration, hydrolysis, oxidation, and ph

thus increase the shelf life of drugs. It was reported that CD-induced enhancement of drug stability inhibition of drug interaction with vehicles and/or inhibition of drug bioconversion at the absorption

molecular shield, CD complexation encapsulates labile drug molecules at the molecular level and thus

various degradation processes.

CYCLODEXTRIN PROPERTY DRUG

HP--CD, DM--CD Photostability Promethazine

-CD Thermal stability in solid state Diclofenac sodium

HP--CD Stability against hydrolysis Digoxin

-CD Photoreactivity Flutamide

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APPLICATIONS OF CDs

Oral Drug Delivery include improvement of drug bioavailability due to increased drug solubility, improvement of rate and extent of dis

of the drug at the absorption site, e.g. the gastrointestinal tract (GIT) or in formulation, reduction of drug-induce

masking .

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APPLICATIONS

Parenteral Drug DeliveryCD derivatives such as amorphous HP-- and SBE--CDs have been widely investigated for parenteral use on account of their hi

minimal toxicity. Applications of CDs in parenteral delivery are solubilization of drugs, reduction of drug irritation at the s

stabilization of drugs unstable in the aqueous environment.

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APPLICATION

Ocular Delivery Applications of CDs in aqueous eye drop preparations include solubilization and chemical stabilization o

ocular drug irritation, and enhancement of ocular drug permeability.

DRUG CYCLODEXTRIN

Acetazolamide HP--CD, -CD, HP--CD

Diclofenac HP--CD, M--CD

Pilocarpine HP--CD, -CD, -CD,

Dexamethasone HP--CD

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APPLICATIONS

Nasal Drug Delivery CDs are effective excipients in nasal drug delivery. CDs improve nasal drug absorption either by increa

solubility and/or by enhancing nasal drug permeability. CDs can also be used to reduce the nasal toxici

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APPLICATIONS

Rectal Drug Delivery Applications of CDs in rectal delivery include enhancing drug absorption from a suppository base either by enhancing drug re

by increasing drug mucosal permeability, increasing drug stability in the base or at the absorption site, providing sustained

alleviating drug-induced irritation. CDs enhance rectal drug stability either by inhibiting the drug/vehicle interaction (by makin

oleaginous base) or by inhibiting the drug bioconversion in the rectum. -CD improved the rectal bioavailability of morphine b

movement of the drug from areas impacted by first pass metabolism.

RECTUM

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APPLICATIONS

Controlled Drug Delivery CDs, due to their ability either to complex drugs or to act as functional carrier materials in pharmaceuti

serve as potential candidates for efficient and precise delivery of required amounts of drugs to targeted

period of time. -CD derivatives are classified as hydrophilic, hydrophobic, and ionizable derivatives. T

derivatives improve the aqueous solubility and dissolution rate of poorly soluble drugs, while the hydro

retard the dissolution rate of water-soluble drugs from vehicles.

RELEASE PATTERN AIM USE OF CD

Delayed, pH-dependent

release

(Enteric) Acid protection of

drugs

CME--CD

Site-specific release Colon-targeting Drug/CD conjugate

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APPLICATION

Colon-Specific Drug DeliveryCDs are barely hydrolyzed and only slightly absorbed in the stomach and small intestine but are absorbed

after fermentation into small saccharides by colonic microbial flora. The peculiar hydrolyzing property

useful for colon drug targeting. Biphenyl acetic acid (BPAA) prodrugs for colon-specific delivery w

conjugation of the drug onto one of the primary hydroxyl groups of -, -, and -CDs through an est

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APPLICATION

Peptide and Protein Delivery Various problems associated in practical use of therapeutic peptides and proteins are the

enzymatic instability, poor absorption through biological membranes, rapid plasma cleararesponse curves, and immunogenicity. CDs, because of their bioadaptability in pharmaceability to interact with cellular membranes, can act as potential carriers for the delivery ofpeptides, and oligonucleotide drugs

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APPLICATION

Dermal and Transdermal Delivery CDs have been used to optimize local and systemic dermal drug delivery. Applications of CDs in transdermal drug delive

of drug release and/or permeation, drug stabilization in formulation or at absorptive site, alleviation of drug-induced locdrug release from vehicle, and alteration of drug bioconversion in the viable skin. CDs, by enhancing apparent drug soluthermodynamic activity in vehicles and thus cause enhancement of drug release from vehicles. The enhancement of dr

by CDs in turn enhances the dermal drug absorption by improving the drug availability at the lipophilic absorptiv

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APPLICATION

Brain Drug Delivery or Brain Targetting: The very low penetration across the BBB greatly hinders the therapeutic use of peptides, and whenever unexplainable poor p

the role of the efflux pumps should be examined. It was reported that P-gpmediated peptide transport may play an importanthe peptide delivery to the central nervous system in vivo. It was also indicated that CDs such as DM--CD, due to their inhib

function, may enhance drug delivery to brain.

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APPLICATIONS

CD Applications in the Design of Some Novel Delivery

Liposomes,Microspheres,Microcapsules,Nanopart

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cyclodextrins ashwani goyal

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