1

PRESENTATION
ON
CYCL DEXTRINS
AS EXCIPIENTS

PRESENTED BY: ASHWANI GOYAL

M.PHARMACY 1ST SEMESTER
DEPARTMENT OF PHARMACEUTICS
CHITKARA SCHOOL PHARMACY
 INTRODUCTION
2

EXCIPIENTS
1.WHAT ARE EXCIPIENTS?
2.WHY WE USE EXCIPIENTS?
3.WHAT TYPE OF EXCIPIENTS ARE USED IN
PHARMACEUTICALS?
 EXCIPIENTS
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EXCIPIENTS BINDE
R

DISINTEGR
An excipient is an inactive substance used as a carrier ANT
for the active ingredients of a medication.

LUBRICAN
In many cases, an "active" substance (such T
as aspirin) may not be easily administered
and absorbed by the human body
DILUENT

Example: Binders,
Disintegrants, Diluents,
Flavours,Cyclodextrins.
 TYPES OF EXCIPIENTS
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Antiadherents Binders Coatings Disintegrants

USED to reduce Binders hold the tablet ingredients from dissolve when wet Fillers and diluents
the adhesion between ingredients in a tablet deterioration by moisture causing the tablet to break fill out the size of a tablet
the powder (granules) together apart

Lubricants
Glidants
Flavours Colours improve the Prevent ingredients from Preservatives
promote powder flow by
used to mask unpleasant appearance of a clumping together and PRESERVE THE
reducing interparticle
tasting active ingredients formulation from sticking to the tablet FORMULATION
friction
punches
 CYCL DEXTRINS
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 1.WHAT ARE CYCLODEXTRINS?

 2.HOW THEY ARE DISCOVERED?
 3.WHAT IS THE PRESENT STATUS OF CDs?
 4.HOW THEY ARE PRODUCED?
 5.WHAT IS THE USE OF CDs IN
PHARMACEUTICALS?
 CYCL DEXTRINS
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 DEFINATION:
CDs are cyclic oligosaccharides derived from
starch containing six (αCD), seven (βCD), eight
(γCD), nine (δCD), ten (εCD) or more (α-1,4)-
linked α-D-glucopyranose units.
 HISTORY
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In 1891 a French scientist, A. Villiers,

described a bacterial digest that he had
isolated from starch.
results indicated that the substance
was a dextrin
Later Franz Schardinger, described two
crystalline compounds α-dextrin and β-
dextrin
Schardinger identified β-dextrin as
Villiers' “cellulosine”
Now these compounds are commonly
called cyclodextrins
 TYPES OF CDs
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CDs

NATURAL SYNTHETIC

Sulfobutylether-β-
α-, β-, and γ-CDs
CD Methyl-β-CD
COMMERCIAL AVAILABILITY
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The world's first CD-containing pharmaceutical product,

prostaglandin E2/βCD (Prostarmon E™sublingual tablets),
was marketed in Japan in 1976.
Twelve years later, the first European CD-based
pharmaceutical product, piroxicam/βCD (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 formulations
In these pharmaceutical products, CDs are mainly used as
complexing agents to increase the aqueous solubility of
poorly water-soluble drugs, to increase their bioavailability
and stability
SOME MARKETED CDs BASED
P’CEUTICALS.
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Drug/cyclodextrin Trade name Formulation Company (Country)

Alpha Cyclodextrin

Alprostadil Caverject Dual i.v. solution Pfizer (Europe)

Cefotiam-hexetil HCl Pansporin T Tablet Takeda (Japan)

β-Cyclodextrin (βCD)

Nimesulide Nimedex Tablets Novartis (Europe)

 STRUCTURE AND PRODUCTION
OF CDs.
11

Due to the chair

conformation of the
glucopyranose units, the
CDs take the shape of a
truncated cone or torus
rather than a perfect
cylinder.
 STRUCTURE
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γ-cyclodextrin- 7 sugar molecules β-cyclo-dextrin- 6 sugar molecules α-cyclodextrin- 5 sugar molecules

Secondary Hydroxyl rim

 PRODUCTION
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Bacillus Circulans
The source of cyclodextrins

Treatment of starches with amylase from B. macerans

gives a crude mixture of αCD (∼60%), βCD (∼20%) and
γCD (∼20%) together with small amounts of CDs with
more that 8 glucopyranose units.
In reaction vats at pH 6.0-7.0 at 35-40 °C.
 TOXOLOGICAL
CONSIDERATIONS
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CONSIDERED
SAFE
 REGULATORY
STATUS
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βCD 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). αCD is similarly listed in the
Ph.Eur., USP/NF and JPC and γCD is
referenced in the JPC and will soon be
included in the Ph.Eur
 ROLE OF CDs
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IN P’CEUTICALS
CYCLODEXTRINS EFFECT THE FOLLOWING
PROPERTIES
1.Effect on
Drug Solubility and Dissolution
Playing a very important role in formulation of poorly water-soluble drugs by improving apparent drug solubility and/or
dissolution through inclusion complexation or solid dispersion, by acting as hydrophilic carriers .
 Examples of CD-enhanced
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Solubility and Dissolution
CYCLODEXTRIN DRUGS
β-CD Nimesulide,
Sulfomethiazole,
Lorazepam, Ketoprofen,
Griseofulvin, Praziquantel,
Chlorthalidone, Etodolac,
Piroxicam,, Itraconazole,
Ibuprofen

α-CD Praziquantel
γ-CD Praziquantel, Omeprazole,
Digoxin
HP-β-CD Albendazole, DY–9760e,
ETH–615, Levemopamil
HCl, Sulfomethiazole,
Ketoprofen,, Griseofulvin,
Itraconazole,
Carbamazepine Zolpidem,
Phenytoin, Rutin
 EFFECT ON DRUG
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BIOAVAILABILITY

CDs enhance the bioavailability of insoluble drugs by increasing the drug solubility, dissolution, and/or drug permeability. CDs
increase the permeability of insoluble, hydrophobic drugs by making the drug available at the surface of the biological barrier,
e.g, skin, mucosa, or the eye cornea, from where it partitions into the membrane without disrupting the lipid layers of the barrier.
 EFFECT ON
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DRUG SAFETY
 CDs have been used to ameliorate the irritation caused by drugs. The increased drug efficacy and potency
(i.e, reduction of the dose required for optimum therapeutic activity), caused by CD-increased drug
solubility, may reduce drug toxicity by making the drug effective at lower doses.
 The toxicities associated with crystallization of poorly water-soluble drugs in
parenteral formulations can often be reduced by formation of soluble drug:CD
complexes.
 EFFECT ON
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DRUG STABILITY
 CDs can improve the stability of several labile drugs against dehydration, hydrolysis, oxidation, and photodecomposition and
thus increase the shelf life of drugs. It was reported that CD-induced enhancement of drug stability may be a result of
inhibition of drug interaction with vehicles and/or inhibition of drug bioconversion at the absorption site. By providing a
molecular shield, CD complexation encapsulates labile drug molecules at the molecular level and thus insulates them against
various degradation processes.

CYCLODEXTRIN PROPERTY DRUG

HP-β-CD, DM-β-CD ↑Photostability Promethazine
β-CD ↑ Thermal stability in solid state Diclofenac sodium

HP-β-CD ↑Stability against hydrolysis Digoxin

β-CD ↑Photoreactivity Flutamide
 APPLICATIONS OF CDs
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Oral Drug Delivery

 include improvement of drug bioavailability due to increased drug solubility, improvement of rate and extent of dissolution, and/ or stability
of the drug at the absorption site, e.g. the gastrointestinal tract (GIT) or in formulation, reduction of drug-induced irritation, and taste
masking .
 APPLICATIONS
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Parenteral Drug Delivery

CD derivatives such as amorphous HP-β- and SBE-β-CDs have been widely investigated for parenteral use on account of their high aqueous solubility and
minimal toxicity. Applications of CDs in parenteral delivery are solubilization of drugs, reduction of drug irritation at the site of administration, and
stabilization of drugs unstable in the aqueous environment.
 APPLICATION
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Ocular Delivery
 Applications of CDs in aqueous eye drop preparations include solubilization and chemical stabilization of drugs, reduction of
ocular drug irritation, and enhancement of ocular drug permeability.

DRUG CYCLODEXTRIN

Acetazolamide HP-β-CD, α-CD, HP-β-CD

Diclofenac HP-β-CD, M-β-CD

Pilocarpine HP-β-CD, α-CD, β-CD,

Dexamethasone HP-β-CD
 APPLICATIONS
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Nasal Drug Delivery

CDs are effective excipients in nasal drug delivery. CDs improve nasal drug absorption either by increasing aqueous drug
solubility and/or by enhancing nasal drug permeability. CDs can also be used to reduce the nasal toxicity of other enhancers
 APPLICATIONS
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Rectal Drug Delivery

 Applications of CDs in rectal delivery include enhancing drug absorption from a suppository base either by enhancing drug release from the base or
by increasing drug mucosal permeability, increasing drug stability in the base or at the absorption site, providing sustained drug release, and
alleviating drug-induced irritation. CDs enhance rectal drug stability either by inhibiting the drug/vehicle interaction (by making the drug insoluble in
oleaginous base) or by inhibiting the drug bioconversion in the rectum. α-CD improved the rectal bioavailability of morphine by inhibiting the upward
movement of the drug from areas impacted by first pass metabolism.

RECTUM
 APPLICATIONS
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Controlled Drug Delivery

 CDs, due to their ability either to complex drugs or to act as functional carrier materials in pharmaceutical formulations, can
serve as potential candidates for efficient and precise delivery of required amounts of drugs to targeted site for a necessary
period of time. β-CD derivatives are classified as hydrophilic, hydrophobic, and ionizable derivatives. The hydrophilic
derivatives improve the aqueous solubility and dissolution rate of poorly soluble drugs, while the hydrophobic derivatives
retard the dissolution rate of water-soluble drugs from vehicles.
RELEASE PATTERN AIM USE OF CD

Delayed, pH-dependent (Enteric) Acid protection of CME-β-CD

release drugs

Site-specific release Colon-targeting Drug/CD conjugate

 APPLICATION
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Colon-Specific Drug Delivery

CDs are barely hydrolyzed and only slightly absorbed in the stomach and small intestine but are absorbed in the large intestine
after fermentation into small saccharides by colonic microbial flora. The peculiar hydrolyzing property of CDs makes them
useful for colon drug targeting. Biphenyl acetic acid (BPAA) prodrugs for colon-specific delivery were developed by
conjugation of the drug onto one of the primary hydroxyl groups of α-, β-, and γ-CDs through an ester or amide linkage.
 APPLICATION
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Peptide and Protein Delivery

 Various problems associated in practical use of therapeutic peptides and proteins are their chemical and
enzymatic instability, poor absorption through biological membranes, rapid plasma clearance, peculiar dose
response curves, and immunogenicity. CDs, because of their bioadaptability in pharmaceutical use and
ability to interact with cellular membranes, can act as potential carriers for the delivery of proteins,
peptides, and oligonucleotide drugs
 APPLICATION
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Dermal and Transdermal Delivery

 CDs have been used to optimize local and systemic dermal drug delivery. Applications of CDs in transdermal drug delivery include enhancement
of drug release and/or permeation, drug stabilization in formulation or at absorptive site, alleviation of drug-induced local irritation, sustaining of
drug release from vehicle, and alteration of drug bioconversion in the viable skin. CDs, by enhancing apparent drug solubility, enhance the drug
thermodynamic activity in vehicles and thus cause enhancement of drug release from vehicles. The enhancement of drug release from vehicles
by CDs in turn enhances the dermal drug absorption by improving the drug availability at the lipophilic absorptive barrier surface
 APPLICATION
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 Brain Drug Delivery or Brain Targetting:

 The very low penetration across the BBB greatly hinders the therapeutic use of peptides, and whenever unexplainable poor peptide absorption is seen
the role of the efflux pumps should be examined. It was reported that P-gp–mediated peptide transport may play an important role in greatly reducing
the peptide delivery to the central nervous system in vivo. It was also indicated that CDs such as DM-β-CD, due to their inhibitory effect on P-gp efflux
function, may enhance drug delivery to brain.
 APPLICATIONS
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 CD Applications in the Design of Some Novel Delivery Systems

Liposomes,Microspheres,Microcapsules,Nanoparticles
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