Solid-State Stability and Preformulation Study of a New Parenteral Cephalosporin Antibiotics (E1040)

Ashizawa, Kazuhide; Uchikawa, Kiyohiko; Hattori, Teiichi; Ishibashi, Yasuo; Miyake, Yasuo; Sato, Takuro

doi:10.1248/yakushi1947.110.3_191

Cited by 4 publications

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“…22) Thus stabilization studies were conducted in order to improve the stability of amorphous of TAK-599 free form. However, our results indicated that the addition of inorganic salts, sugars and amino acids as reported by Ashizawa et al, 13) was ineffective at stabilizing TAK-599, and it was therefore necessary to investigate stabilization through crystallization.…”

Section: Stability Of Amorphous Tak-599mentioning

confidence: 48%

“…Some methods have been reported for the stabilization of injectable formulations such as chemical interaction with additives 13) and crystallization of API. 22) Thus stabilization studies were conducted in order to improve the stability of amorphous of TAK-599 free form.…”

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%

“…There have been a number of publications describing alterations of physicochemical properties with changes in crystallinity; for example, hygroscopicity, [3][4][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) 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.…”

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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: 48%

Section: Stability Of Amorphous Tak-599mentioning

confidence: 99%

mentioning

confidence: 99%

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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Investigation of optimal manufacturing process for freeze-dried formulations: Observation of frozen solutions by low temperature X-ray diffraction measurements

2005

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Sterile Parenteral Products: A Narrative Approach

Dongare

Mali

Patrekar

2015

J. Drug Delivery Ther.

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One of the first group"s toaddress these patient safety issues was the NationalCoordinating Committee on Large Volume Parenteral (NCCLVP). Parenteral medications are products which are introduced in a manner which circumvents the body"s most protective barriers, the skin and mucous membranes, and, therefore, must be "essentially" free of biological contamination. Most are injected or placed into the body tissues and do not pass thru the liver before entering the bloodstream. This can include injections, topical and inhalation routes. Generally in pharmacy, parenteral refers to injection and the topical and inhalation routes are separated into their own routes of administration. NCCLVP was established by the US Pharmacopeia Convention, Inc., and subsequently developedand recommended standards of practice for the preparation, labeling, and quality assurance of hospital pharmacyadmixture services. Parenteral administration of drug is often critical and associated with problems such as limited number of acceptable excipients, stringent requirements of aseptic production process, safety issues, and patient noncompliance. Still this route maintains its value due to special advantages like quicker onset of action in case of emergency; target the drug quickly to desired site of action, prevention of first pass metabolism etc. This review highlightsformulation of parenteral product and advanced techniques involved in parenteral products.

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Solid-State Stability and Preformulation Study of a New Parenteral Cephalosporin Antibiotics (E1040)

Cited by 4 publications

References 0 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

Investigation of optimal manufacturing process for freeze-dried formulations: Observation of frozen solutions by low temperature X-ray diffraction measurements

Sterile Parenteral Products: A Narrative Approach

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