Enhanced Oral Bioavailability of Vinpocetine Through Mechanochemical Salt Formation: Physico-Chemical Characterization and In Vivo Studies

Hasa, Dritan; Voinovich, Dario; Perissutti, Beatrice; Grassi, Mario; Bonifacio, Alois; Sergo, Valter; Cepek, Cinzia; Chierotti, Michele R.; Gobetto, Roberto; Dall’Acqua, Stefano; Invernizzi, Sergio

doi:10.1007/s11095-011-0415-8

Cited by 34 publications

(30 citation statements)

References 27 publications

(31 reference statements)

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“…A similar behavior takes place in nanocrystalline and amorphous drug (amorphous state may be considered as a crystal of vanishing dimensions) that, upon dissolution, tend to return to the more thermodynamically stable microcrystal condition [58,[60][61][62]. Notably, recrystallization implies a reduction of drug solubility, this being of paramount importance with regard to drug bioavailability [63]. Typically, solid drug dissolution may be modeled according to the following equation [64]:…”

Section: Mesh Size Determinationmentioning

confidence: 99%

Mathematical Modeling of Drug Release from Natural Polysaccharides Based Matrices

Chiarappa

Abrami²,

Dapas³

et al. 2017

Natural Product Communications

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The new concept of personalized medicine and the affirmation of Nucleic Acid Based Drugs (NABDs), an emerging class of bio-drugs constituted by short sequences of either DNA or RNA, represent a new challenge for the mathematical modelling in the drug delivery and adsorption field. Indeed, whether patient uniqueness asks for the use of theoretical tools enabling a rational approach adapting to each patient, NABDs delivery brings to our attention new aspects of drug delivery due to the NABDs fragile nature and way of action. This review aims to present and discuss the mathematical modelling of drug release from natural polysaccharides matrices with particular care to the description of the chemical and physical phenomena ruling drug delivery.

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Section: Mesh Size Determinationmentioning

confidence: 99%

Mathematical Modeling of Drug Release from Natural Polysaccharides Based Matrices

Chiarappa

Abrami²,

Dapas³

et al. 2017

Natural Product Communications

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“…38 The mechanical energy and shearing forces generated in the mill allow solid-state reactions to be conducted. 18 A summary of the various solid-state forms of ciprofloxacin discussed in this manuscript is presented in Table 1. …”

Section: Production Of Crystalline and Amorphous Saltsmentioning

confidence: 99%

“…17 Hasa et al obtained a rapidly and highly absorbed amorphous salt, vinpocetine citrate, by neat co-grinding a mix of the drug and the acid in the presence of amorphous polymer, crospovidone. 18 Consequently, the aim of this work was to explore the possibility of crystalline ciprofloxacin salt formation with succinic acid with an emphasis on screening whether this drug molecule can form salts with multiple stoichiometries. Also, considering that only very limited information on pharmaceutically-relevant properties of amorphous salts can be found, to manufacture the amorphous counterparts of any ciprofloxacin succinate form(s) and compare the physicochemical properties of the various forms.…”

Section: Introductionmentioning

confidence: 99%

Formation and Physicochemical Properties of Crystalline and Amorphous Salts with Different Stoichiometries Formed between Ciprofloxacin and Succinic Acid

Paluch¹,

McCabe²,

Müller‐Bunz

et al. 2013

Mol. Pharmaceutics

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Multi-ionisable compounds, such as dicarboxylic acids, offer the possibility of forming salts of drugs with multiple stoichiometries. Attempts to crystallise ciprofloxacin, a poorly water soluble, amphoteric molecule with succinic acid (S) resulted in isolation of ciprofloxacin hemisuccinate (1:1) trihydrate (CHS-I) and ciprofloxacin succinate (2:1) tetrahydrate (CS-I). Anhydrous ciprofloxacin hemisuccinate (CHS-II) and anhydrous ciprofloxacin succinate (CS-II) were also obtained. It was also possible to obtain stoichiometrically equivalent amorphous salt forms, CHS-III and CS-III, by spray drying and milling, respectively, of the drug and acid. Anhydrous CHS and CS had melting points at ~215 and ~228 °C, while the glass transition temperatures of CHS-III and CS-III were ~101 and ~79 °C, respectively. Dynamic solubility studies revealed the metastable nature of CS-I in aqueous media, resulting in a transformation of CS-I to a mix of CHS-I and ciprofloxacin 1:3.7 hydrate, consistent with the phase diagram. CS-III was observed to dissolve non-congruently leading to high and sustainable drug solution concentrations in water at 25 and 37 ºC, with the ciprofloxacin concentration of 58.8±1.18 mg/ml after 1 hour of the experiment at 37 ºC. This work shows that crystalline salts with multiple stoichiometries and amorphous salts have diverse pharmaceutically-relevant properties, including molecular, solid state and solubility characteristics.

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“…Indeed, most of the drugs are optimized solely on the basis of their pharmacological activity and not for what concerns bioavailability. Examples of commonly marketed drugs that are poorly soluble in water (less than 100 g/cm 3 [13]) include non-steroidal anti-inflammatory drugs (NSAIDs), anticholesterol, antimycotics, antibiotics, anticonvulsants, chemotherapeutics, antivirals, β-blockers, calcium channel blockers and immunosuppressants [4,[14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Dissolution of an ensemble of differently shaped poly-dispersed drug particles undergoing solubility reduction: mathematical modelling

et al. 2020

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<p class="ADMETabstracttext">The aim of this theoretical paper is to develop a mathematical model for describing the dissolution process, in a finite liquid environment, of an ensemble of poly-dispersed drug particles, in form of sphere, cylinder and parallelepiped that can undergo solubility reduction due to phase transition induced by dissolution. The main result of this work consists in its simplicity as, whatever the particular particles size distribution, only two ordinary differential equations are needed to describe the dissolution process. This, in turn, reflects in a very powerful and agile theoretical tool that can be easily implemented in electronic sheets, a widespread tool among the research community. Another model advantage lies on the possibility of determining its parameters by means of common independent techniques thus enabling the evaluation of the importance of solid wettability on the dissolution process.</p>

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Enhanced Oral Bioavailability of Vinpocetine Through Mechanochemical Salt Formation: Physico-Chemical Characterization and In Vivo Studies

Abstract: From the in vivo studies on rats the obtained salt was four times more bioavailable than its physical mixture and bioequivalent to the commercial salt produced by conventional synthetic process implying the use of solvent.

Cited by 34 publications

References 27 publications

Mathematical Modeling of Drug Release from Natural Polysaccharides Based Matrices

Mathematical Modeling of Drug Release from Natural Polysaccharides Based Matrices

Formation and Physicochemical Properties of Crystalline and Amorphous Salts with Different Stoichiometries Formed between Ciprofloxacin and Succinic Acid

Dissolution of an ensemble of differently shaped poly-dispersed drug particles undergoing solubility reduction: mathematical modelling

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