The delayed release formulation can be obtained by the use of enteric type cyclodextrins such as O – carboxymethyl – O –ethyl- b cyclodentrin and their derivatives in different areas of drug delivery, particularly in parenteral,oral,ophthalmic, nasal, dermal, rectal, sublingual, pulmonary and other novel drug delivery systems are explained in detail.

CHARACTERISTICS OF β-CYCLODEXTRIN DERIVATIVES:

Among the compounds, hydrophilic cyclodextrins such as HP-β-CD, SBE- b - CD, and branched b-CD have received special attention, because their toxicity is very low and aqueous solubility is very high, promising a parenteral use^22-27. The glucuronyl – glucosyl - b - CD (GUG - b - CD) is a new entry of branched CD, which contains a carboxyl group in the branched maltosyl residue²⁸. In fact, the hemolytic activity of GUG - b - CD on rabbit erythrocytes is lower than that b- CD. Table 1 Contains the pharmaceutically useful b- CD derivatives classified in to hydrophilic,hydrophobic and ionic derivatives.^29-32

b-CYCLODEXTRIN EFFECTS ON IMPORTANT DRUG PROPERTIES IN FORMULATION:

1. Effect on drug solubility and dissolution:

The cydodextrin has been playing a very important role in formulation of poorly water soluble drugs by improving the apparent durg solubility and dissolution through inclusion complexation or solid dispersion. Out of various commercially available CDs, methylated CDs with a relatively low molar substitution appear to be the most powerful solubilizers. Reduction of drug crystallinity on complaxation or solid dispersion with CDs also contributes to the CD increased apparent drug solubility and dissolution rate^{33, 34}. CDs, as a result of their ability to form in situ inclusion complaxes in dissolution medium, can enhance drug dissolution even when there is no complexation in the solid state³⁵. SBE -b-CD was shown to be an excellent solubilizer for several drugs and was more effective than b - CD but not –as effective as DM- b-CD³⁶.

2. Effect on drug bioavailability:

The cyclodextrin enhances the bioavailability of insoluble drugs by increasing its drug solubility, dissolution and drug permeability. This is achieved 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 disturbing the lipid layers of the barriers. At low RM- b-CD concentrations, when hydrocortisone was in suspension, increasing the CD concentration increased the drug flux. At higher CD concentrations, when the drug was in solution, increasing the CD concentration decreased the flux³⁷. It was found that addition of polymers can further enhance the drug permeability from aqueous CD solutions. Carboxy methyl cellulose (CMC) enhanced triclosan bioavailability from toothpastes containing b- CD by forming a drug /CD/ CMC complex with improved substantivity³⁸. CDs increased the bioavailability of lipophilic itraconazole from both an oral solution and an intravenous formulation by improving the drug solubility and absorption³⁹.

3. Effect on drug safety:

Cyclodextrins have been used to ameliorate the irritation caused by drugs⁴⁰. The increased drug efficacy and potency, caused by cyelodextrian increased drug solubility, may reduce drug toxicity by mixing the drug effective at lower doses. The studies shows that the b - CD enhanced antiviral activity of ganeclelovir on human cytomegalo virus clinical strains and the resultant increase in the drug potency has reduced the drug toxicity⁴¹. Inclusion complexation with HP-b- CD reduced the side effects of 2 ethyl- haxyl-P-dimethyl aminobenzoate (auvfilter) by limiting the interaction of the UV filter with skin⁴². In a study with patients, piroxicam / b - CD inclusion complex showed better tolerance with lower incidence and severity of gastrointestinal side effects compared with the fine drug⁴³.

4. Effect on drug stability:

Cyclodextrins can improve the stability of several labile drugs against dehydration, hydrolysis, oxidation and photodecomposition and thus increase the shelf life of drugs. By providing a molecular shield, CD complaxation encapsulates labile drug molecules at the molecular level and thus insulates them against various degradation processes. SBE - b-CD showed greater stability enhancement of many chemically unstable drugs than other CD³⁶.

H-b-CD significantly reduced the photo degradation of 2 – ethyl hexyls p-dimethyl aminobenzoate in solution than in emulsion vehicle⁴², CDs improved the photostability of trimeprazine (when the solution pHis reduced)⁴⁴and promethazine⁴⁵. Table 2 summarizes the different drugs that are marketed as β –cyclodextrene complexes.

β–CYCLODEXTRIN APPLICATION IN DRUG DELIVERY:

1. COLON SPECIFIC DRUG DELIVERY:

Colon targeting is essentially classified as a delayed release with fairly long lag time, because the time required reaching the colon after oral administration is expected to be about 8 hours in man. When a cyclodextrin complex is orally applied, it readily dissociates in the gastrointestinal fluid, depending on the magnitude of the stability constant. This indicates that cyclodextrin complex is not suitable for colon specific delivery as the drug is released, because of the dilution and competitive inclusion effects, before it reaches the colon. One of the advantages of the cyclodextrin drug conjugate is that it can survive passage through stomach and small intestine, but the drug release will be triggered by enzymatic degradation of cyclodextrines in the colon. Cyclodextrin conjugates of nonsteroidal anti –inflammatory drug, biphenylylacetic acid (BPAA)⁴⁶^-48 and ketoprofen⁴⁹, a short – chain fatty acid, n – butylic acid⁵⁰ and a steroidal drug, prednisolone^51-54, anticipating new candidates for colon – specific delivery prodrugs. The drug molecules were selectively conjugated on to the primary or secondary hydroxyl groups of cyclodextrins through an ester or an amide – linkage, respectively, and their physicochemical properties and drug release behavior in various solutions were investigated. The anti – inflammatory effect of BPAA system was evaluated using the model of carrageenam induced acute edema in rat paw. In the case of BPAA / b-CD complex, a rapid anti inflammatory response was observed, compared to drug alone, because the drug was mainly absorbed from the small intestine after a fast dissolution of the complex. Complexation of triamcinolone actonide (TA) with b-CD improved the sphericity of microcrystalline cellulose (MCC) - b - CD-TA spherical pellets (5:90:5) prepared by extrusion and spheronization for colon targeting. TA complication with the CD also facilitated the application of coating resistant to gastric and small intestinal media and maintained the pellet integrity in dissolution medium with no premature bursting of coatings on granule swelling⁵⁵.

2. DERMAL DRUG DELIVERY:

Cyclodextrins have a significant safety margin in dermal application and can be used to optimize the transdermal delivery of drugs intended either for local or systemic use. They also improves the solubility and stability of drugs in the topical preparations, enhances the transdermal absorption of drugs, sustains the drug release from the vehicle and avoids undesirable side effects associated with dermally applied drugs. The main barrier for dermal drug absorption through the skin is the outer most layer stratum corneum. Penetration enhancers like alcohols, fatty acids etc. are used to decrease its barrier properties. The cyclodextrins enhance drug delivery through aqueous diffusion barrier but not through lipophlic barriers like stratum corneum. Diffusion rate of ketoprofen from its b - CD and HP – B – CD inclusion complexes was in the order of carbopol gel > oil / water emulsion > fatty ointment⁵⁶. Hydrophilic cyclodextrins improve the release rate of lipophilic drugs from hydrophilic aqueous vehicle. Hydrophilic CDs markedly increased the in vitro release rate of corticosteroid from aqueous base but retard the same from non aqueous bases. Complexation with b , DM - b and HP-b -CDs increased the release of 4- biphenyl acetic acid from hydrophilic ointment. b and HP - b - CDs significantly enhanced the anti-inflammatory effects of indomethacin in hydroxyethyl cellulose hydrogels in healthy volunteers⁵⁷. Hydrophilic b and HP - b - CDs enhanced the release of hydrocortisone from oil / water cream and hydro-gel but retarded the same from petrolatum vehicle or water/oil cream⁵⁸. Complexation with cyclodextrins was suggested to be a rational way to improve physicochemical properties of drugs for transdermal delivery. b and HP - b - CDs increased the skin permeability of dexamithasone and also improved its stability in skin by protecting it against skin metabolism⁵⁹. HP - b - CDs increased the amount of piroxicam transported through skin but pretreatment of skin with the CD showed no effect on drug retention in skin. Hence the cyclodextrin effect on the drug’s skin permeability was reported to be due to increased drug concentration in gel and not due to enhancement of drug iontophoretic flux⁶⁰. Hydrophobic cyclodextrins can modulate drug release from vehicles. Nitroglycerin compilation with DE- b - CD accelerated the drug release rate from ointments but the same with b - CD retarted the drug release. Hence a combination of the drug complex with DE-β-CD and b-CD was suggested to obtain sustained release percutaneous preparations of the drug⁶¹.

3. RELEASE CONTROL OF WATER SOLUBLE DRUGS:

Cyclodextrins , 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 . b - 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. Hence hydrophilic and hydrophobic cydodextrin derivatives are used in immediate and prolonged release type formulation respectively. Among the alkylated CDs , DE- b and TE-b-CDs were the first used slow release carriers and their hydrophobic complexes with diltiazem⁶² and isosoride dinitrate⁶³ provided slow drug release on oral administration in dogs. Quaglia et al⁶⁴ reported that CDs can be used to modulate drug delivery from swellable systems, eg, b - CD significantly affected the delivery of nicardipine from swellable crosslinked polyethylene glycol matrix by decreasing effective diffusivity through the matrix. Directly compressed tablets containing prednisolone with SBE -b - CD and polymer physical mixture showed more enhanced drug release than the control (with lactose instead of CD) due to formation of an in situ drug : CD complex in the gel layer⁶⁵. To maintain a prolonged efficacy of nifedipine, some extent of initial burst before slow release is necessary to provide more balanced oral bio availability. On the basis of these goals, suitable formulation of double – layer tablets containing fast – release portion and slow release portion was surveyed⁶⁶. In the fast release portion amorphous nifedipine power prepared by spray – drying with HP - b-CD and small amounts of non ionic surfactant HCO – 60 were employed to attain an initial rapid dissolution and to prevent the crystal growth during the storage. In the slow – release portion, hydroxy propylcellulose (HPC) with different viscosity grades were employed to provide an appropriate sustained release of poorly water – soluble drug from the viscous matrices. The double layer tablet consisting of HP - b - CD with 3 % HCO – 60/ (HPC – low; HPC medium) in a weight ratio 1 / (1.5 : 1.5) was selected as an appropriate modified release formulation because it elicited almost comparable retarding effects with superior oral bio availability compared with those of a commercially available slow release nifedipine product⁶⁶.

4. PARENTERAL DRUG DELIVERY:

Cyclodextrin derivatives such as amorphous HP - b and SBE - b- CD have been widely investigated for parenteral use on account of their high aqueous solubility and minimal toxicity, HP - b - CD with much higher aqueous solubility allows potential administration of various drugs with no significant toxicity problems and hence is more often used in parenteral formulations. Kurkov et al⁶⁷ evaluated in vitro the competitive binding of drugs between human serum albumin (HSA) and HP - b - CD in isotonic pH 7.4 phosphate buffer solution at ambient temperature. Protein binding of drugs that are both strongly protein bound and have high affinity to HP - b - CD is most likely to be affected by parentaly administered HP-β-CD. Weekly protein bound drugs and drugs with low affinity towards HP - b - CD are insensitive to the cyclodextrin presence regardless their lipophilic properties.

6. NASAL DRUG DELIVERY:

In order to enter systemic circulation the drug has to dissolve in the aqueous nasal fluids. In nasal formulations, cyclodextrines are normally used to increase the aqueous solubility of lipophillic drugs. Cho et al⁷⁶developed an intranasal delivery system of fexofenadine hydrochloride(FXD,HCl), a new formulation using poloxamer 407/ HP-β-CD based thermoreversible gels with chitosan to enhance permeation and solubility. After intranasal permeation of P407/ HP-β-CD based thermoreversible gels containing 0.1% and 0.3% of chitosan in rabbits at 0.5mg/kg dose, plasma concentration of FXD HCl were significantly higher than those of nasal solutions (P<0.05). In particular, the bioavailability of the optimized thermoreversible gel containing 0.3% chitosan was about 18 fold higher than that of the solution type. Rathnam et al⁷⁷ investigated the nasal absorption of progesterone from carbapol based nasal gels in rabbits. The potential use of β-CD as nasal absorption enhancer by simple addition, as a physical mixture and as a complex with progesterone was investigated. Cyclodextrin complex promotes the nasal asorption of progestrone from carbapol gels as compared with gels where the cyclodextrin is added by simple addition and gels which do not contain cyclodextrin . Midazolam was absorbed rapidly when administered as an aqueous nasal spray (pH 4.3) containing SBE-β-CD (14%w/v), HPMC (0.1%w/v), and other additives⁷⁸. Cyclodextrines can also be used to reduce the nasal toxicity of other enhancers without affecting their absorption enhancing property. β-CD or DM-β-CD reduced the serious nasal toxicity of sodium deoxycholate by inhibiting the leucine aminopeptidase activity in nasal mucosa without affecting the absorption enhancing property of the bile salt for insulin⁷⁹.

Jug et al⁸⁰ developed a cyclodextrin based nasal delivery system for lorazepam. The in vitro dissolution studies demonstrated that the microparticles containing the lorazepam inclusion complex displayed 1.8-2.5 times faster drug release compared with those containing free lorazepam.

7. RECTAL DRUG DELIVERY:

The release of drug from suppository bases is one of the important factors in the rectal absorption of the drugs, since the rectal fluid is small in volume and viscous compared to gastro intestinal fluid. Drug release from the suppository base is important in rectal absorption because of the high viscosity of rectal fluids. The effect of cyclodextrins on rectal drug absorption can be influenced by partition coefficient of the drug and its CD complex, magnitude of the complex stability constant, and nature of suppository base.

In general, hydrophilic cyclodextrins enhances the release of poorly water soluble drugs from oleaginous suppository bases because of the lesser interaction of the complexes with the vehicles. The complexation of lipophillic drugs with hydrophilic cycldextrins make them insoluble in hydrophobic vehicles, the complex existing as well-dispersed fine particles in the vehicles. Rectal absorption of flurbiprofen and biphenyl acetic acid was improved DM-β-CD and HP-β-CD, respectively. Cyclodextrins may not affect drug release if the drug/CD complex dissociates in the vehicle itself. For example, although the dissociation rate of ethyl 4-phenylyl acetate (EBA) was highest from the DM-β-CD complex, only the HP-β-CD complex enhanced EBA release from the oleaginous suppository base because of lower dissolution of the HP-β-CD complex in the vehicle.

8. PEPTIDE AND PROTEIN DELIVERY:

Advances in biotechnology have allowed the economical and large scale production of therapeutically important peptide and protein drugs to be used to combat poorly controlled diseases. The rapid progress in molecular biology however has not been matched by the progress in the formulation and development of delivery systems for such next generation drugs. Many attempts have addressed these problems by chemical modifications or by co-administration of adjuncts to eliminate undesirable properties of peptide and protein drugs such as chemical and enzymatic instability, poor absorption through biological membranes, rapid plasma clearance, and immunogenicity. Cyclodextrins, because of their bioadaptibility in pharmaceutical use and ability to interact with cellular membranes, can act as potential carriers for the delivery of proteins, peptides, and oligonucleotide drugs.

Schulze et al⁸¹developed lipid based implants for proteins by twin screw extrusion as a manufacturing strategy. Using lipid blends of low and high melting lipids, extrusion could be performed at moderate temperatures. In addition to the lipids, the implant systems contained 10% rh-interferon alpha-2a (2 FN-alpha) co-lyophilized with HP-β-CD, and 10% or 20% PEG, respectively. Interestingly, extrudates with a smaller diameter revealed a continuous release profile with a burst, lags and linear release phase lasting over 13 to 26 days.

Chen et al⁸² investigated the use of chitosan in combination with the ionic additives sulfobutyl-ether-7-beta-cyclodextrin (SB-CD) or SB-CD/dextran sulfate(SB-CD/DS) mixture in comparision with chitosan: DS in the formulation of nanoparticles incorporating the hexapeptide dalagin. The use of either DS or SB-CD/DS mixture produced chitosan nanoparticles with small particle size high dalagin entrapment efficiency, enhanced peptide stability, and sustained release characterstics. Sajeesh et al⁸³developed an oral insulin delivery system based on HP-β-CD-insulin complex encapsulated polymethacrylic acid-chitosan-polyether nanoparticles. Cyclodextrin complexed insulin encapsulated mucoadhesive nanoparticles appear to be a good candidate for oral insulin delivery.

DM-β-CD (5%) enhanced the intranasal calcitonin absorption in rats and rabbits. In rabbits the intranasal absorption was comparable to intravenous or subcutaneous calcitonin absorption. In rabbits, a nasal spray of liquid and powder formulation of glucagons containing DM-β-CD provided improved bioavailability (78%) of glucagons compared with their subcutaneous administration. The absolute bioavailability of insulin in rats was also increased to ~100% on nasal administration with DM-β-CD (3-5%)⁸⁴. β-CD or DM-β-CD reduce the serious nasal toxicity of sodium deoxycholate (a bile salt) by inhibiting the leucine aminopeptidase activity in the nasal mucosa without affecting the absorption enhancing property of the bile salt for insulin⁷⁹. β-CD improved insulin loading of alginate microspheres prepared by an emulsion based process. The process was suggested to be useful in the development of oral insulin from optimized microsphers was found to take place from the GI region⁸⁵.

9. GENE DELIVERY:

Gene therapy requires carriers that can efficiently and safely transfer the gene into the nucleus of the desired cells. There are two categories of gene therapy vectors, i.e., viral vectors and non viral vectors. The non viral vectors have many advantages over viral vectors, such as easy of manufacture, safety, low immunogenicity, and molecular attachment of targeting ligand⁸⁶. However the problem is that the efficiency of non viral vector mediated gene transfer to the cell is markedly low compared to the viral vectors.

Bellocq et al⁸⁷prepared new synthetic biocompatible materials that deliver a protein to cultured cells via the use of an adenoviral delivery vector. The synthetic construct consist of a linear, β-CD containing polymer and an ademantane-based cross linking polymer. When the two polymers are combined, they create an extended network by the formation of inclusion complexes between the cyclodextrins and adamantanes. Fibroblast imposed to these construct show proliferation rates and migration patterns similar to those obtained with collagen. Gene delivery (green fluorescent protein) to fibroblasts via the inclusion of adenoviral vectors in the synthetic construct is equivalent to levels observed with collagen. Pun et al⁸⁸ prepared CD-IPEI and CD-bPEI by grafting linear and branched poly (ethyleneimines), IPEI and bPEI, with β-CD. The cyclodextrin containing polycations, when combined with adamantine- poly (ethylene glycol) (AD-PEG) conjugates, form particle that are stable at physiological salt concentrations. Tail vein injections into mice of 120 microgram of plasmid DNA formulated with CD-IPEI and AD-PEG do not reveal observable toxicities, and both nucleic acid accumulation and expression are observed in liver. Neutral and amphiphilic as well as cationic CDs have been used for synthesis of novel gene delivery vectors. Neutral CDs like β, DMβ, and HP-β-CDs were reported to increase DNA cellular uptake by increasing its permeability. The increased DNA permeability was reported to be a result of interaction of the CDs with membrane components such as cholesterol but not due to their complexing ability for DNA. Cationic polyamino CDs, because of their polycationic polyanionic interaction with mononeucleotides, neutralized the multiple changes on DNA and thus made DNA compact into a particle of suitable size for cellular internalization.

10. LIPOSOMES DELIVERY:

The main purpose of liposomal drug delivery is to combine the advantages of cyclodextrin such as increased drug solubility with the advantages of liposome such as drug targeting. Liposomes entrap hydrophilic drugs in the aqueous phase and hydrophobic drugs in the lipid bilayers and retain drugs enroute to their destination. Bragagni et al⁸⁹studied the effect of complexation with HP-β-CD anesthetic efficacy of liposomal formulation of prilocaine. Cyclodextrin complexation not only allowed an efficient encapsulation of prilocaine base in the aqueous vesicle core, but also increased the anesthetic effect duration and reduced the initial lag time, in comparison with the corresponding formulations containing respectively, free prilocaine in the lipophilic phase or prilocaine hydrochloride in the aqueous vesicle core. The technique of double loading was the most effective, giving rise to the shortest onset time and longest duration of anesthetic effect. Chakraborty et al⁹⁰evaluated therapeutic and hemolytic effects of liposomal preparation derived from prolipasome entrappig inclusion complex of amphotericin B (Am B) with the chemically modified β-CD. The liposomal Am B-HPβCD and Am B-SBβCD found to be 6 times less toxic than free Am B or conventional liposomal Am B. Experimental findings indicate that infected animals treated with Am B entrapped inclusion complexes significantly reduced CFU values (fungal counts), where as infected with conventional liposome or free Am B showed insignificant reduction in CFU. Liposomal entrapment can also alter the pharmaceutics of inclusion complexes. Liposomal entrapment drastically reduced the urinary loss of HP-β-CD/ drug complexes but augmented the uptake of the complexes by liver and spleen, where after liposomal disintegration in tissues, drugs were metabolized at rates dependent on the stability of the complexes^91,92. Selection of CD can also have significant effect on the amount of drug associated with vesicles than β-CD. However, HP-β-CD, as a result of its ability to get entrapped in high amounts in the vesicles, also showed a higher velocity of destabilizing effect on vesicles than β-CD⁹³. Complexation with CDs can improve the stability of liposomes, eg most stable liposomal formulations of metronidazole and verapamil were obtained by direct spray drying of lipid, drug and HP- β-CD mixture⁹⁴.

11. MICROSPHERE DELIVERY SYSTEMS:

The role of cyclodextrins in microsphere preparation was first studied by Loftsson⁹⁵. Nifedipine release from chitosan microsphere was showed down a complexation with HP- β-CD inspite of the improved drug loading efficiency. Since it is highly unlikely for CD molecules to diffuse out of the microspheres, even with a low stability constant, the complex must first release the free drug that can permeate out of the microspheres. Hence the observed slow nifedipine release from the microspheres was reported to be due to lesser drug availability from the complex and also due to formation of hydrophilic chitosan/ CD matrix layer around the lipophilic drug that further decreases the drug matrix permeability⁹⁶. Maestrelli et al⁹⁷ prepared microspheres for colonic delivery of ketoprofen- HP- β-CD complex. Permeation studies showed an increased permeation of the drug formulated as microspheres, particularly marked when it was used as complex, thus revealing an enhancing power of both cyclodextrin and chitosan with a synergistic effect in improving drug permeation. Study of in vivo release behavior of β-CD from β-CD/ polyacrylic acid (PAA) microspheres, prepared by a water/ oil solvent evaporation technique, indicated a high encapsulating efficiency (99%) with potential covalent binding of the CD⁹⁸.

12. NANOPARTICLES DELIVERY SYSTEMS:

Nanoparticles are considered more stable than liposomal delivery systems. Nanoparticles are stable systems suitable to provide targeted drug delivery and to enhance the efficacy and bioavailability of poorly soluble drugs. However the safety and efficacy of nanoparticles are limited by their very low drug loading and limited entrapment efficiency that may lead to excessive administration of polymeric material. Cyclodextrins are used for this reason to improve water solubility and sometimes the hydrolytic or photolytic stability of drugs for better loading properties. Drug/ cyclodextrin complexes act to solubilize or stabilize active ingredients within the nanoparticles, resulting in increased drug concentration in the polymerization medium and increased hydrophobic sites in the nanosphere structure when large amount of CD are associated to the nanoparticles. Addition of steroid drugs, hydrocortisone (HC), and progesterone (PN) as β-CD or HP- β-CD complexes maintained the sizes of solid lipid nanoparticles (SLN) below 100 nm with the steroids dispersed in an amorphous state . Cyclodextrin complexation increased the incorporation of the more hydrophilic drug, HC than PN but provided lower release of both the drugs from SLN compared with the release from SLN containing the free drugs. It was suggested that the process of incorporating drugs partly in free form and partly in the complexed form may be used to modulate release kinetics of drugs from SLN⁹⁹.

CONCLUSION:

Cyclodextrins, as a result of their complexation ability and other versatile characteristics, are containing to have different applications in different areas of drug delivery and pharmaceutical industry. In the beginning cyclodextrins were used to enhance water solubility and chemical stability of drugs and these functionalities were related to their ability to form drug/cyclodextrin inclusion complexes. However, in recent year’s cyclodextrin have been shown to participate in various types of non-inclusion complexes with, for example, organic salts and water soluble polymers. Moreover, the most desirable attribute for the drug carrier is its ability to deliver a drug to a targeted site. The conjugates of a drug with cyclodextrins can be a versatile means if constructing a new class of novel drug delivery systems like liposome, microsphere, peptide delivery and gene delivery.

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Received on 21.12.2010

Accepted on 25.12.2010

Research Journal of Pharmaceutical Dosage Forms and Technology. 2(6): Nov.-Dec. 2010, 361-369

Category	Cyclodextrin	Characteristics	Use
Hydrophilic derivatives	Methylated -b - CD DM- b -CD TM -b -CD	Soluble in cold water and in organic solvents. Surface active, hemolytic.	Oral, dermal, mucosal
	Hydroxyalkylated b -CD 2-HE - b-CD 2-HP-b-CD 3-HP-b-CD 2,3 –DHP -b -CD	Amorphous mixture with different degrees of substitution , highly water soluble (>50%), low toxicity.	Oral , dermal, Mucsal, parented (intravenous )
	Branched b-CD G1-b-CD G2- b-CD Gll G -b-CD	Highly water soluble (>50%), low toxicity.	Oral, mucosal, parental (intravenous)
Hydrophobic derivatives	Alkylated b-CD DE-b-CD TE- b-CD	Poorly water soluble in organic solvents, surface active.	Oral , parentual (subcutaneous) (slow release )
Hydrophobic derivatives	Acylated b-CD TA- b -CD TV -b -CD	Poorly water soluble, soluble in organic solvents, film formation.	Oral , dermal (slow release)
Ionizable derivatives	CME -b- CD b- CD-Sulphate SBE-β-CD β –CD-phosphate	pKa = 3 to 4, soluble at pH> 4, pKa>1, water soluble	Oral , dermal mucosal (delayed release)

Cyclodextrin	Drug	Trade name	Dosage Form
b - cyclodentrin	Benexate Hcl	Lonmiel	Capsule
	Cephalosporin	Meiact	Tablet
	Dexamethasone	Glymesason	Ointment
	Diphenhydramin Hcl	Stada – travel	Chewing tablet
	Iodine	Mena Gargle	Solution
	Nicotine	Nicogum	Sublingual tablet
	Nimesulide	Nimedex	Tablet
	Nitroghycerine	Nitropen	Sublingul tablet
	Omeprazol	Omebeta	Tablet
2-Hydroxypropyl-b-cyclodentrin	Cisapride	Propulsid	Suppository
	Itralonazole	Sporanox	Oral and IV solutions
	Mitomycin	Mitozytrex	IV infusion
Methylated b- cyclodextrin	Chloramphenicol	Clorocil	Eye drop solution
	17 b-estradiol	Aerodiol	Nasal spray
Sulfobutylether b- cyclodentrin	Voriconazole	Vfend	IV solution
	Ziprasidone mesylate	Zeldox	IM solution

β-Cyclodextrin and Its Derivatives Based Drug Delivery

Tapan Kumar Giri*, Manish Desmukh, Animesh Jaiswal and Dulal Krishna Tripathi

Rungta College of Pharmaceutical Sciences and Research, Kohka Road, Kurud, Bhilai-491024, India.