Polymer/Amorphous Salt Solid Dispersions of Ciprofloxacin

Mesallati, Hanah; Tajber, Lidia

doi:10.1007/s11095-017-2250-z

Cited by 31 publications

(22 citation statements)

References 36 publications

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“…Stabilizers of the first category, consisting of low molecular weight compounds such as: acetylated sugars [9,13], organic acids [14][15][16], or even different drugs [17][18][19][20][21][22], have proved to be very effective in inhibiting recrystallization. However, the vast majority of stabilizers are large molecular weight compounds (the second group), such as polymers [5,7,[23][24][25][26][27][28]. The main reason for this is the variety of the possible applications of the latter.…”

Section: Introductionmentioning

confidence: 99%

Enhancement of the Physical Stability of Amorphous Sildenafil in a Binary Mixture, with either a Plasticizing or Antiplasticizing Compound

et al. 2020

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The main purpose of this paper was to evaluate the impact of both high- and low-Tg polymer additives on the physical stability of an amorphous drug, sildenafil (SIL). The molecular mobility of neat amorphous SIL was strongly affected by the polymeric excipients used (Kollidon VA64 (KVA) and poly(vinylacetate) (PVAc)). The addition of KVA slowed down the molecular dynamics of amorphous SIL (antiplasticizing effect), however, the addition of PVAc accelerated the molecular motions of the neat drug (plasticizing effect). Therefore, in order to properly assess the effect of the polymer on the physical stability of SIL, the amorphous samples at both: isothermal (at constant temperature—353 K) and isochronal (at constant relaxation time—τα = 1.5 ms) conditions were compared. Our studies showed that KVA suppressed the recrystallization of amorphous SIL more efficiently than PVAc. KVA improved the physical stability of the amorphous drug, regardless of the chosen concentration. On the other hand, in the case of PVAc, a low polymer content (i.e., 25 wt.%) destabilized amorphous SIL, when stored at 353 K. Nevertheless, at high concentrations of this excipient (i.e., 75 wt.%), its effect on the amorphous pharmaceutical seemed to be the opposite. Therefore, above a certain concentration, the PVAc presence no longer accelerates the SIL recrystallization process, but inhibits it.

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Section: Introductionmentioning

confidence: 99%

Enhancement of the Physical Stability of Amorphous Sildenafil in a Binary Mixture, with either a Plasticizing or Antiplasticizing Compound

et al. 2020

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“…Amorphous salts of CIP containing succinic acid or amino acids as counterions have also been prepared. While these formulations were far more soluble than the CIP ASDs, they were less stable when exposed to high humidity and in most cases decreased the permeability of the drug [10,11].…”

Section: Introductionmentioning

confidence: 99%

Fluoroquinolone Amorphous Polymeric Salts and Dispersions for Veterinary Uses

2019

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Enrofloxacin (ENRO) is a poorly soluble drug used in veterinary medicine. It differs from the more widely used fluoroquinolone ciprofloxacin (CIP) by the presence of an ethyl substituent on its piperazine amino group. While a number of recent studies have examined amorphous composite formulations of CIP, little research has been conducted with ENRO in this area. Therefore, the main purpose of this work was to produce amorphous solid dispersions (ASDs) of ENRO. The solid-state properties of these samples were investigated and compared to those of the equivalent CIP ASDs, and their water uptake behavior, solubility, dissolution, and antibacterial activity were assessed. Like CIP, X-ray amorphous solid dispersions were obtained when ENRO was ball milled with acidic polymers, whereas the use of neutral polymers resulted in semi-crystalline products. Proton transfer from the carboxylic acids of the polymers to the tertiary amine of ENRO’s piperazine group appears to occur in the ASDs, resulting in an ionic bond between the two components. Therefore, these ASDs can be referred to as amorphous polymeric salts (APSs). The glass transition temperatures of the APSs were significantly higher than that of ENRO, and they were also resistant to crystallization when exposed to high humidity levels. Greater concentrations were achieved with the APSs than the pure drug during solubility and dissolution studies, and this enhancement was sustained for the duration of the experiments. In addition, the antimicrobial activity of ENRO was not affected by APS formation, while the minimum inhibitory concentrations and minimum bactericidal concentrations obtained with the APS containing hydroxypropyl methylcellulose acetate succinate grade MG (HPMCAS-MG) were significantly lower than those of the pure drug. Therefore, APS formation is one method of improving the pharmaceutical properties of this drug.

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“…5 Salt formation changes the state of CIP molecules in their crystal form from zwitterionic to cationic, effectively reducing the lattice energy and improving aqueous solubility. 6 Therefore, a number of efforts have been made to extend the range of fluoroquinolone solid forms and to modify the poor solubility performance of CIP and NFX through salt preparation with different organic acids, including aliphatic [7][8][9][10][11][12] and aromatic carboxylic acids, [13][14][15][16] derivatives of sulfonic acids, and artificial sugars. [17][18][19][20] Recently, a new drug-drug multicomponent solid consisting of two antibacterial agents, namely norfloxacin and sulfathiazole, has been obtained.…”

Section: Introductionmentioning

confidence: 99%

Diversity of crystal structures and physicochemical properties of ciprofloxacin and norfloxacin salts with fumaric acid

et al. 2018

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adThe crystallization of norfloxacin and ciprofloxacin -antibacterial fluoroquinolone compounds -with fumaric acid resulted in the isolation of six distinct solid forms of the drugs with different stoichiometries and hydration levels. Each salt can be selectively obtained by mechanochemical treatment in the presence of water/organic mixtures of a particular composition. The new phases were analysed using TG, DSC and PXRD, and their structural parameters were determined using single crystal X-ray diffraction. Despite having the same counterion, the ciprofloxacin and norfloxacin fumarates crystallise to form distinct crystal structures, which consequently determine the differences in the relative stability and the corresponding physicochemical properties of the solid forms. The influence of water activity (a w ) on the solid form stability and transformation pathways of anhydrous and hydrated fumarates was elucidated. The solubility and phase stability of the salts were also investigated in pharmaceutically relevant buffer solutions with pH 6.8 and pH 1.2. The largest solubility improvement relative to the parent drug (≈33 times) in the pH 6.8 medium was observed in the case of ciprofloxacin hemifumarate sesquihydrate. In turn, the norfloxacin fumarates showed a moderate 3-fold enhancement in solubility.

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Polymer/Amorphous Salt Solid Dispersions of Ciprofloxacin

Cited by 31 publications

References 36 publications

Enhancement of the Physical Stability of Amorphous Sildenafil in a Binary Mixture, with either a Plasticizing or Antiplasticizing Compound

Enhancement of the Physical Stability of Amorphous Sildenafil in a Binary Mixture, with either a Plasticizing or Antiplasticizing Compound

Fluoroquinolone Amorphous Polymeric Salts and Dispersions for Veterinary Uses

Diversity of crystal structures and physicochemical properties of ciprofloxacin and norfloxacin salts with fumaric acid

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