Dehydration effect on the stability of cefixime trihydrate

Kitamura, Satoshi; Koda, Shinobu; Miyamae, Akira; Yasuda, Tsutomu; Morimoto, Yukiyoshi

doi:10.1016/0378-5173(90)90112-h

Cited by 42 publications

(43 citation statements)

References 9 publications

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“…However, stability is often affected by moisture content and in particular degradation reactions are reported to be accelerated by the destruction of the crystalline structures of hydrates. 16,28) Moisture adsorption and desorption isotherms of TAK-599 at 25°C are shown in Fig. 7.…”

Section: Stability Of Amorphous Tak-599mentioning

confidence: 99%

“…There have been a number of publications describing alterations of physicochemical properties with changes in crystallinity; for example, hygroscopicity, 3-5) crystalline transition, 6) dehydration of crystalline water, 7,8) dissolution rate 9,10) and heat of solution 11,12) studies have all been reported. Although numerous studies regarding stability and stabilization have been reported for cephalosporin antibiotics, which are often physicochemically unstable in the solid state, [13][14][15][16] there are not many reports that discuss the relationship between crystallinity and stability. 7,17,18) …”

mentioning

confidence: 99%

“…Although numerous studies regarding stability and stabilization have been reported for cephalosporin antibiotics, which are often physicochemically unstable in the solid state, [13][14][15][16] there are not many reports that discuss the relationship between crystallinity and stability. 7,17,18) TAK-599 (ceftaroline fosamil) [(6R,7R)-7-({(Z)-2-(ethoxyimino)-2-[5-(phosphonoamino)-1,2,4-thiadiazol-3-yl]-acetyl} amino)-3-{[4-(1-methyl-4-pyridinio)-1,3-thiazol-2-yl]thio}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate acetic acid solvate] is a novel N-phosphono type aqueous prodrug of T-91825 that has strong anti-methicillin resistant Staphylococcus aureus (MRSA) activity (Fig. 1).…”

mentioning

confidence: 99%

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Stability and Stabilization Studies of TAK-599 (Ceftaroline Fosamil), a Novel N-Phosphono Type Prodrug of Anti-methicillin Resistant Staphylococcus aureus Cephalosporin T-91825

Ikeda

Ban

Ishikawa

et al. 2008

CHEMICAL & PHARMACEUTICAL BULLETIN

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Generally, most active pharmaceutical ingredients (APIs) used in oral dosage formulations are developed as crystalline forms rather than amorphous materials, since it is easier to control batch quality, impurity levels and maintain stability. [1][2][3] On the other hand, amorphous APIs typified by lyophilized powders are often preferred to improve solubility in injectable formulations, although the amorphous substance is generally less stable than the crystalline substance.Formulation design based on physicochemical considerations is important for development to maintain the appropriate level of quality and stable supply required for a pharmaceutical. There have been a number of publications describing alterations of physicochemical properties with changes in crystallinity; for example, hygroscopicity, 3-5) crystalline transition, 6) dehydration of crystalline water, 7,8) dissolution rate 9,10) and heat of solution 11,12) studies have all been reported. Although numerous studies regarding stability and stabilization have been reported for cephalosporin antibiotics, which are often physicochemically unstable in the solid state, [13][14][15][16] there are not many reports that discuss the relationship between crystallinity and stability. 7,17,18) acid solvate] is a novel N-phosphono type aqueous prodrug of T-91825 that has strong anti-methicillin resistant Staphylococcus aureus (MRSA) activity (Fig. 1). 19,20) Since TAK-599 had not been crystallized in a free form in the early research stage, we attempted to develop the compound as an amorphous solid. However amorphous of TAK-599 free form was unstable even when stored cold, and was difficult to develop as a pharmaceutical agent.After numerous attempts at crystallization, crystalline TAK-599, acetic acid solvate was crystallized from aqueous acetic acid solution, and the key factors for the stability affecting the stability of TAK-599 were identified by a stability study on TAK-599 crystals. It was found that the crystallinity of TAK-599 and moisture content affected stability in the solid state. In this paper, we report that both sufficient crystallinity and rigorous moisture control are crucial to maintain the quality of TAK-599 in the long term. TAK-599 (known as ceftaroline fosamil) is a novel N-phosphono type prodrug of a cephalosporin compound, T-91825, that exhibits strong activity against methicillin resistant Staphylococcus aureus (MRSA). The stability and stabilization of TAK-599 were investigated by kinetic analysis focused on crystallinity and moisture content. Initially it was planned to develop TAK-599 as an injectable formulation using the amorphous solid powder prepared by lyophilization. However, amorphous of TAK-599 free form was found to be chemically unstable even when stored at 8°C, and thus development was focused on the crystalline material. After exhaustive screening of crystallization condition, the monoacetic acid solvate was found to yield TAK-599 in a crystalline form. Physicochemical properties were studied to identify the key factors ...

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Section: Stability Of Amorphous Tak-599mentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Stability and Stabilization Studies of TAK-599 (Ceftaroline Fosamil), a Novel N-Phosphono Type Prodrug of Anti-methicillin Resistant Staphylococcus aureus Cephalosporin T-91825

Ikeda

Ban

Ishikawa

et al. 2008

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…The determination of the polymorphism of a substance is of great importance due to the strong influence of the crystalline form on the physicochemical properties, bioavailability and stability of drugs [92], and, in some compounds with biological activity, can even become metastable forms, being twice as active as the stable form [93]. So, our research group has carried out the study of the physicochemical properties of polymorphic forms of a serie of alkylimidothio-and alkylimidoselenocarbamate derivatives with a combination of DSC, thermomicroscopy and X-ray diffractometry [94].…”

Section: Alkylimidothio-and Alkylimidoselenocarbamatesmentioning

confidence: 99%

Thermal Analysis of Sulfur and Selenium Compounds with Multiple Applications, Including Anticancer Drugs

Plano¹,

Palop²,

Sanmartín³

2013

Applications of Calorimetry in a Wide Context - Differential Scanning Calorimetry, Isothermal Titration Calorimetry and Microca

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“…The following are known to be techniques for determining the content of amorphous substances: Powder X-ray diffraction (XRD), 12) IR 13) or near infra-red spectroscopy (NIRS), 14) thermal analyses, such as specific heat capacity (C p ) at glass transition point (T g ) 15) and DSC, 16) and solid-state NMR. 17) However, there have been few reports concerning the content of amorphous substance in formula.…”

Section: )mentioning

confidence: 99%

Quantitative Determination of Amorphous Nicardipine Hydrochloride in Long Acting Formula (NIC-LA) Using Light Anhydrous Silicic Acid

Kohinata

Fujii²,

Nakamura³

et al. 2004

CHEMICAL & PHARMACEUTICAL BULLETIN

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Nicardipine hydrochloride (NIC) is a calcium channelblocking agent that is effective in the treatment of mild to moderate hypertension, angina pectoris and cerebral disease. However, its conventional formulation undergoes rapid absorption and extensive biotransformation in the liver, and has a short elimination half-life (about 90 min) 1) Plasma NIC concentration often fluctuates significantly and adverse reactions such as syncope are consequently induced. Thus, for the purpose of alleviating adverse reactions due to over-absorption and improving dosing compliance, we investigated on the development of the long-acting formula of NIC-LA ® . Sustained release formulations have already been developed for several drugs, and the following formulation techniques have been used: combining large amounts of a substance that hardly disintegrates in stomach or intestines, coating granules and tablets with a hydrophobic additive, coating a drug with a semipermeable membrane, and formation of a solid dispersion system with insoluble or hydrophilic polymer substances by means of mixing, adsorption and/or binding. 2)However, in the case of drugs like NIC, which is very insoluble in intestinal fluid, the above techniques merely reduce the bioavailability and cannot be expected to realize sustained release of the drug. Thus, Yuksel et al. have investigated formula to regulate the release of NIC in the stomach and to increase the solubility in intestinal fluid.3-5) Ohmura et al., on the other hand, have focused on the fact that the solubility in intestinal fluid is 43 to 47 mg/ml for amorphous NIC and 5 to 8 mg/ml for crystal NIC, and they found that sustained release could be obtained by making NIC amorphous without adding any excipients, thereby improving solubility in intestinal fluid.6) Based on this notion, the NIC-LA ® formula was developed, and by controlling the ratio of crystal NIC and amorphous NIC in this formula, suitable NIC plasma levels can be maintained (C max ϭ0.8 h and 6.0 h, and the elimination half-lifeϭ7.6 h), even when the frequency of administration is reduced. 6,7)Drugs can be made amorphous by procedures such as grinding, lyophilization, spray drying, fusion and solvent evaporation.8-10) Ohmura et al. developed the NIC-LA ® by mixing enteric granules consisting of 100% amorphous NIC prepared by a vibration ball mill and conventional gastric granules consisting of 100% crystal NIC at a ratio of 7 : 3. 6)The amorphous NIC content of this formula, which affects the efficacy and safety of NIC-LA ® , can be confirmed by controlling the quantities of gastric granules and enteric granules during the formulation process. On the other hand, in the NIC-LA ® formula developed by Shibahara et al., the sustained release granules, which are obtained by drying a suspension of light anhydrous silicic acid (LASA) and carboxy methylethylcellulose (CMEC) in a 20% aqueous ethanol solution dissolving about 40% of crystal NIC, were used as enteric granules, and these granules were coated with pulverized sustained release granu...

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Dehydration effect on the stability of cefixime trihydrate

Cited by 42 publications

References 9 publications

Stability and Stabilization Studies of TAK-599 (Ceftaroline Fosamil), a Novel N-Phosphono Type Prodrug of Anti-methicillin Resistant Staphylococcus aureus Cephalosporin T-91825

Stability and Stabilization Studies of TAK-599 (Ceftaroline Fosamil), a Novel N-Phosphono Type Prodrug of Anti-methicillin Resistant Staphylococcus aureus Cephalosporin T-91825

Thermal Analysis of Sulfur and Selenium Compounds with Multiple Applications, Including Anticancer Drugs

Quantitative Determination of Amorphous Nicardipine Hydrochloride in Long Acting Formula (NIC-LA) Using Light Anhydrous Silicic Acid

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