Crystal Structure Changes of γ-cyclodextrin After the SEDS Process in Supercritical Carbon Dioxide Affect the Dissolution Rate of Complexed Budesonide

Toropainen, Tarja; Heikkilä, Teemu; Leppänen, Jukka; Matilainen, Laura; Velaga, Sitaram P.; Jarho, Pekka; Carlfors, Johan; Lehto, Vesa‐Pekka; Järvinen, Tomi; Järvinen, Kristiina

doi:10.1007/s11095-006-9227-7

Cited by 33 publications

(37 citation statements)

References 27 publications

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“…[24][25][26][27] Therefore, the diffraction patterns of the a-and g-CyD polypseudorotaxanes with the pegylated insulin were indexed on the basis of the two-dimensional hexagonal and tetragonal unit cells with dimensions aϭbϭ27.44 Å and aϭbϭ24.02 Å, respectively, as shown in Table 2 were used to calculate the unit cell dimensions (Fig. 2).…”

Section: Resultsmentioning

confidence: 99%

Polypseudorotaxane Formation of Randomly-Pegylated Insulin with Cyclodextrins: Slow Release and Resistance to Enzymatic Degradation

Higashi

Hirayama

Misumi

et al. 2009

CHEMICAL & PHARMACEUTICAL BULLETIN

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NotesPegylation technology is one of the useful methods for sustained release systems, because when poly(ethylene glycol) (PEG) is covalently attached to a protein, it transfers many of the polymer's favorable characteristics to the resulting conjugate, i.e. a number of benefits such as increased circulating half-life, enhanced proteolytic resistance, reduced antigenicity and immunogenicity, reduced aggregation, and improved bioavailability, etc. There are many examples of protein conjugates that are mono-or randomly-substituted with PEG, such as adenosine deamidase, insulin, interferona2, b-lactoglobulin, a-chymotrypsin, lipase, bovine liver catalase, asparaginase, and superoxide dismutase, etc. of which the first three conjugates are on the market.1-3) Most of commercially available pegylated drugs are randomly-substituted derivatives, because of synthetic difficulty of the mono-pegylation.Supramolecular assemblies have attracted a great amount of attention, due to its intriguing topologies and its application in various fields such as nanodevices, sensors, molecular switches, and drug delivery systems, etc. Cyclodextrins (CyDs) are cyclic oligosaccharides composed of 6 (a-CyD), 7 (b-CyD), and 8 (g-CyD) glucopyranose units and can form inclusion complexes with various organic and inorganic compounds.4) Harada et al. first reported the supramolecular assemblies of PEG and a-CyD, in which a number of the cyclic molecule are spontaneously threaded onto the polymer chain.5,6) These complexes are called polypseudorotaxanes, because the CyD can be dethreaded from the polymer chain when dissolved in water. Recently, many studies on CyD polypseudorotaxanes with various polymers were reported, e.g. blanched PEG, poly(ethylene imine) and poly(lactic acid), etc. [7][8][9] In addition, a number of applications of polypseudorotaxanes as a biomaterial were reported, e.g. gene delivery carrier, 10-13) biodegradable hydrogel 11,[14][15][16][17] and galectin binding material. 18) In previous studies, 19,20) we found that the mono-substituted pegylated insulin forms polypseudorotaxanes with a-and g-CyDs in a similar manner as PEG does. However, there are no evidences if randomly-or multiply-pegylated proteins form polypseudorotaxanes with CyDs. In this study, therefore, we prepared randomly-substituted pegylated insulin and its CyD polypseudorotaxanes and evaluated it as a sustained release system. Further, proteolytic behavior of insulin in the polypseudorotaxane was investigated. ExperimentalMaterials Bovine Zn-insulin (27.5 IU/mg, approximately 0.5% Zn) was obtained from Sigma Chemicals (St. Louis, MO, U.S.A.). a-Succinimidyloxysuccinyl-w-methoxy-polyoxyethylene (MW about 2300) was obtained from NOF Co. (Tokyo, Japan). CyDs were donated by Nihon Shokuhin Kako (Tokyo, Japan). All other materials were of reagent grade, and deionized double distilled water was used.Preparation of Randomly-Pegylated Insulin Randomly-pegylated insulin was synthesized according to the modified method of Hinds et al. 3,21) Briefly, insulin (MW 5734...

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Section: Resultsmentioning

confidence: 99%

Polypseudorotaxane Formation of Randomly-Pegylated Insulin with Cyclodextrins: Slow Release and Resistance to Enzymatic Degradation

Higashi

Hirayama

Misumi

et al. 2009

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…Drug References geraniol, mustard oil [12] acetaminophen [13] piroxicam [14,15] miconazole [15,16,17,18,19,20] Eflucimibe [21,22] ibuprofen [23,24,25,26,27,28,29] naproxen [28,30,31,32] flurbiprofen [28] citral, thymol, carvacrol [33] imazalil [34] salicylic acid [35] azobenzene [36] budesonide [37,38,39] indomethacin [40] polyaniline [41] cholesterol [42] arylphosphines [43] itraconazole [44,45,46] 2 sodium salts [47] hydroxyflavone [48] benzocaine [50, 49,] bupivacaine, and mepivacaine [50] simvastatin [51] several triphenyl phosphine derivatives [52] all-trans-lycopene [53] 15 carbohydrates [54] human serum immunoglobulin G …”

Section: Resultsmentioning

confidence: 99%

Preparation of inclusion complex of piroxicam with cyclodextrin by using supercritical carbon dioxide

Sauceau

Rodier

Fages

2008

The Journal of Supercritical Fluids

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“…The diffraction pattern of the co-precipitate corresponded to that of the tetragonal columnar form of g-CD. [19][20][21][22] This indicated the complex formation of FBP with g-CD.…”

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Simultaneous Dissolution of Naproxen and Flurbiprofen from a Novel Ternary .GAMMA.-Cyclodextrin Complex

Higashi

Ideura

Waraya

et al. 2010

CHEMICAL & PHARMACEUTICAL BULLETIN

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A crystalline ternary complex was prepared by sealed-heating of naproxen (NPX) with a flurbiprofen (FBP)/g g-cyclodextrin (g g-CD) inclusion complex. The dissolution rates of NPX and FBP in the ternary complex were almost the same, indicating that FBP and NPX from the complex dissolved simultaneously. The ternary CD complex showing a fascinating dissolution property could be a new formulation for combination therapies.Key words cyclodextrin; dissolution; powder X-ray diffraction; sealedheating; inclusion complex Many drug candidates usually show poor water solubility. Various pharmaceutical techniques such as polymorphic control, co-crystal formation, and nanoparticle preparation are available to improve the physicochemical properties of drugs.1-4) Cyclodextrin (CD) inclusion complex formation is also a useful technique for improving the dissolution property and enhancing the bioavailability of drugs.5-7) Co-precipitation, freeze-drying, evaporation, co-grinding, and processing with supercritical CO 2 are used for the preparation of solid CD inclusion complexes. [8][9][10] We have prepared various types of solid CD inclusion complexes by using the sealed-heating method wherein a mixture of guest and CD molecules is simply heated within an enclosed space. [11][12][13] In the sealed-heating method, vaporized guest molecules are assumed to be included in the cavity of CDs through the gas phase. Crystalline inclusion complexes of poorly water-soluble drugs can be obtained through the sealed-heating method without using solvents. Specific inclusion complexes that are difficult to prepare can also be obtained through this method. In our recent study, it was found that the sealed-heating of salicylic acid (SA) with polyethylene glycol (PEG)/g-CDpolypseudorotaxane induced complex formation.14) In this complex, two SA molecules for each g-CD molecule were incorporated into the intermolecular spaces between the columns of g-CD stacks, while double-stranded PEG chains were included in the g-CD cavity. Although a large number of studies have been carried out on the inclusion complexes of CDs, there are only a few reports on the existence of guest molecules outside the CD cavity. [15][16][17][18] New CD complexes with desired properties can be designed if the interstitial spaces outside the CD cavity are utilized for the incorporation of guest drugs. In this study, a ternary g-CD complex containing two active pharmaceutical ingredients (APIs) was prepared by the sealed-heating method. Using this method, guest drugs could be incorporated into the intermolecular spaces between g-CD columns. The dissolution property of the obtained complex was studied in order to assess its potential for pharmaceutical applications.Flurbiprofen (FBP) and naproxen (NPX) are anti-inflammatory drugs with poor water solubility (Fig. 1). In this study, each drug was used as a model guest molecule either for inclusion in the g-CD cavity or incorporation into the intermolecular spaces. The preparation process of the ternary complex consisted of two st...

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Crystal Structure Changes of γ-cyclodextrin After the SEDS Process in Supercritical Carbon Dioxide Affect the Dissolution Rate of Complexed Budesonide

Abstract: The crystal structure of gamma-CD and subsequently, the dissolution rate of complexed budesonide, can be modified with the processing conditions.

Cited by 33 publications

References 27 publications

Polypseudorotaxane Formation of Randomly-Pegylated Insulin with Cyclodextrins: Slow Release and Resistance to Enzymatic Degradation

Polypseudorotaxane Formation of Randomly-Pegylated Insulin with Cyclodextrins: Slow Release and Resistance to Enzymatic Degradation

Preparation of inclusion complex of piroxicam with cyclodextrin by using supercritical carbon dioxide

Simultaneous Dissolution of Naproxen and Flurbiprofen from a Novel Ternary .GAMMA.-Cyclodextrin Complex

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