cyclodextrins ashwani goyal
TRANSCRIPT
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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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