Cubic phase gels

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A seminar on Liquid crystal Cubic Phase.:

A seminar on Liquid crystal Cubic Phase. Presented by Ankita D. Chonkar. M.Pharm .(2 nd semester .) i Guided by Mrs. S. R. Hardkar . Asst.Prof.Pharmaceutics P.D.E.A.’s S.G.R.S. College of Pharmacy.Saswad,Pune.


Contents. Liquid crystals Lyotropic liquid crystal phase. Phase transformation of lyotropic liquid crystal. Phase Diagram. Structure of cubic phase. Cubic phase gels as a drug delivery system. Model for Biomembrane. Other macroscopic forms. Application. Characterization . Conclusion. References. Acknowledgement .

What are liquid crystals?:

What are liquid crystals? Liquid crystals (LCs) are the state of matter that have properties between those of a conventional liquid and those of a solid crystal. For instance, Liquid crystal may flow like a liquid, but its molecules may be oriented in a crystal-like way . Liquid crystals can be divided into – Thermotropic Lyotropic M etallotropic phases.

Lyotropic liquid-crystalline phases are abundant in living systems. For example, many proteins and cell membranes are liquid crystals. Lyotropic LC s can be obtained mainly by amphiphilic molecules or block copolymers. :

Lyotropic liquid-crystalline phases are abundant in living systems. For example, many proteins and cell membranes are liquid crystals. Lyotropic LC s can be obtained mainly by amphiphilic molecules or block copolymers. Depending upon the concentration of LC forming agents various self asembled structures can be formed. Discontinuous cubic phase. (micellar cubic phase) H exagonal columnar phase . (middle phase ) Bicontinuous cubic phase. Lamellar phase. Reverse hexagonal columnar phase. Inverse cubic phase (Inverse micellar phase)

Phases of liquid crystal.:

Phases of liquid crystal. Lamellar phase Spherical micelle Bicontinous Cubic phase Hexagonal phase Phases of liquid crystals

Structure of cubic phase:

Structure of cubic phase Cubic phases have an interesting thermodynamically stable structure consisting of curved bicontinuous lipid bilayer in three dimensions, separating two congruent networks of water channels of 5 nm. Curvature energy of each monolayer and stretching energy of each lipid chain, these 2 energy terms are least frustrated simultaneously in cubic phase. c

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Crystal lattice structure of cubic phase .

Cubic phase gels:

Cubic phase gels Able to dissolve or disperse variety of drugs in various concentrations. Sustained release of drug. Enhanced stability profile of some drugs . Biodegradability. Applications in variety of drug delivery systems such as mucosal,periodontal,vaginal,In-situ gel forming parenteral.

Cubic phase as a model for biomembrane:

Cubic phase as a model for biomembrane Cubic phase gel as a model for biomembrane .

Protein drug delivery system.:

Protein drug delivery system. Few oligopeptides such as desmopressin,lysine,vasopressin,somatostatine , Renin inhibitors can be incorporated in cubic phase gels. Cubic phase gels protects the peptides from enzymatic degradation. Retains the native confirmation and biological activity of protein. Can act as in situ enzyme factory. Increased activation of certain enzymes like protein kinase C. Can act as a carrier system for orally administered Apx toxins. Protects the Humalin against agitation induced aggregation. Can act as a encapsulating agent for bovine hemoglobin .

Other macroscopic forms.:

Other macroscopic forms . Cubosomes Usually produced by combining monoolein and water, resulting cubic gel is dispersed into particles via application of mechanical or ultrasonic energy. Hydrotropes like ethanol can be added. Precursor form Can exist as a solid and liquid material that forms the cubic phase in response to stimulus, such as contact with water. Diblock copolymers like plouronics with other excipients after spray drying forms precursor.


Applications. Drug used/category. Cubic phase forming agents Disease condition. Route of administration. Macroscopic form. Propantheline bromide. Antimuscarinic . Glyceryl monooleate . Urinary Incontinence. Vaginal Gel. Metronidazole. Glyceryl monooleate , poloxamer Mouth Infection. Periodontal. Gel. Bupivacaine. Lidocaine . Glyceryl Monooleate . Post surgical Wound. Local. Gel. Tetracycline, Serratiopeptidase . Pluronics, Aerosil . Mouth infection. Periodontal. Gel. Pluronics, Aerosil . Respiratory diseases. Drug delivery via Inhalation. Composite particles, Precursor.


Characterization. Plane polarized microscopy . X-ray diffraction. N eutron diffraction. Dielectric spectroscopy. Dissolution studies.


Conclusion. The unique structure and physicochemical prop erties of liquid crystalline cubic phase gel makes it suitable as a drug delivery matrix but complicating factor is the solubilisation and/or incorporation of the drug molecules in the hydrated bilayer of the amphiphilic monoglyceride , and thus hydrophilic and lipophilic drugs can cause different phase transformations. This could possibly affect the release characteristics of the drug and have an adverse effect on the physical stability of the matrix. of the lipid-water cubic mesophase, Cubic phase may never be able to provide release duration longer than 2–3 days .


References. A.Tardieu, V. Luzzati, Polymorphism of lipids. A novel cubic phase — a cage-like network of rods with enclosed spherical micelles, Biochim. Biophys. Acta (1970) 219 (1) 11–17. Alfons , K., Engstr¨om , S., Drug compatibility with the sponge phases formed in monoolein , water and propyleneglycol or poly(ethylene glycol). J. Pharm. Sci. (1998) 87, 1527–1530. Allababidi , S., Shah, J.C., Kinetics and mechanism of release from glyceryl monostearate -based implants: evaluation of release in a gel simulating in vivo implantation. J. Pharm. Sci. (1998) 87, 738–744. Aota -Nakano, Y., Li, S.J., Yamazaki, M, Effects of electrostatic interaction on the phase stability and structures of cubic phases of monoolein /oleic acid mixtures membranes. Biochim. Biophys. Acta (1999) 1461, 96–102. Arakawa, T., Timasheff , S.N., Mechanism of poly(ethylene glycol) interaction with proteins. Biochemistry (1985) 24, 6756–6762. Brange , J., Havelund , S., Insulin pumps and insulin quality: requirements and problems. Acta Med. Scand.Suppl .( 1983.) 671, 135–138. Brange , J., Langkjær , L.,. Insulin structure and stability.In : Wang, Y.J., Pearlman, R. (Eds.), Stability and Characterization of Protein and Peptide Drugs: Case Histories.Plenum Press, New York, (1993) 315–350. Brennan, J.R., Gebhart , S.S., Blackard , W.G., Pump-induced insulin aggregation. A problem with the Biostator . Diabetes (1985) 34, 353–359.

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Chang, C.M., Bodmeier , R., 1997b. Effect of dissolution media and additives on the drug release from cubic phase delivery systems. J. Control. Release 46, 215–222. Chang, C.M., Bodmeier , R.,. Low viscosity monoglyceride based drug delivery systems transforming into a highly viscous cubic phase. Int. J. Pharm. (1998),173, 51–60. Chawla , A.S., Hinberg , I., Blais , P., Johnson, D., Aggregation of insulin in solution containing surfactants, in contact with different materials. Diabetes (1985.) 34, 420–424. Clogston , J., Rathman , J., Tomasko , D., Walker, H., Caffrey,M ., Phase behaviour of a monoacylglycerol (Myverol18–99 K/water system). Chem. Phys. Lipids (2000).107, 191–220. D’Antona , P., Parker Jr., W.O., Zanirato , M.C., Esposito, E., Nastruzzi , C.,. Rheologic and NMR characterization of monoglyceride -based formulations. J. Biomed. Mater. Res (2000). 40–52. Dash, A.K., Gong, Z., Miller,D.W ., Huai -Yan, H., Laforet , J.P.,.Development of a rectal nicotine delivery system for the treatment of ulcerative colitis. Int. J. Pharm. (1999) 190, 21–34. Dathe , M., Gast , K., Zirwer , D., Welfle , H., Mehlis , B.,.Insulin aggregation in solution. Int. J. Peptide Protein Res. (1990)36, 344–349. Engstr¨om , S., Engstr¨om , L., Phase behaviour of the lidoca´ınemonoolein -water system. Int. J. Pharm. (1992).79, 113–122.

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Geraghty , P.B., Attwood, D., Collett , J.H., Dandiker , Y., The in vitro release of some antimuscarinic drugs from monoolein /water lyotropic liquid crystalline gels. Pharm. (1996) Res. 13, 1265–1271. L . Lynch; Enhanced loading of water-soluble actives into bicontinuous cubic phase liquid crystals using cationic surfactants Journal of Colloid and Interface Science 260 (2003) 404–413 Maheshwari M, Miglani G, Mali A, Paradkar A, Yamamura S, Kadam S. Development of Tetracycline- Serratiopeptidase -Containing Periodontal Gel: Formulation and Preliminary Clinical Study. AAPS Pharm SciTech. 2006; 7(3): Article 76. S. Chandrasekhar Liquid Crystals, Cambridge University Press: 1994 Shah J.; Cubic phase gel as a drug delivery system; Advanced Drug Delivery Reviews 47 (2001) 229–250 Spicer P. Novel Process for Producing Cubic Liquid Crystalline Nanoparticles ( Cubosomes ) Langmuir 2001, 17 , 5748-5756


Acknowledgement. II I would like to pay my sincere gratitude to Principal Dr. Ashok V. Bhosale and University of Pune for conducting this project activity as a part of academic. My sincere thanks to my guide Mrs.S.R.Hardikar. without whose guidance, I would have not been able to complete my project. I would like to thank her for guiding & helping me all the time. I would like to thank all the teachers who have given me inspiration and build up my confidence. I would like to thank all my friends who have supported me at various stages during the preparation of this project.

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Thank you .

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