Amorphous nanoparticle complex of perphenazine and dextran sulfate as a new solubility enhancement strategy of antipsychotic perphenazine

Dong, Bingxue; Hadinoto, Kunn

doi:10.1080/03639045.2017.1287721

Cited by 18 publications

(20 citation statements)

References 22 publications

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“…Perphenazine (PPZ), as a typical antipsychotic, is a lipophilic phenothiazine derivative compound, with a partition coefficient of 4.2 and aqueous solubility of less than 0.1 mg/ml which is mainly metabolized through hepatic pathways. These characteristics result in low bioavailability through oral administration [6][7][8][9]. Although different approaches have been proposed to improve the low oral bioavailability of PPZ, including the development of sublingual solid dispersion [10], fast disintegrating tablets [11], electrospun fibers [12], and ultrafine oil-water emulsions [13], recent developments in nanotechnology offer abundant possibilities for the preparation of more efficient oral drug delivery systems to overcome these problems [14].…”

Section: Introductionmentioning

confidence: 99%

Development of Perphenazine-Loaded Solid Lipid Nanoparticles: Statistical Optimization and Cytotoxicity Studies

Farsani

Mahjub

Mohammadi

et al. 2021

BioMed Research International

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Objective. Perphenazine (PPZ), as a typical antipsychotic medical substance, has the same effectiveness compared to atypical antipsychotic medications for the treatment of schizophrenia. Despite the lipophilic essence, PPZ encounters limited bioavailability caused by the first-pass metabolism following oral administration. In the present study, PPZ-containing solid lipid nanoparticles (PPZ-SLNs) were prepared and optimized based on different factors, including lipid and surfactant amount, to develop appropriate and safe novel oral dosage forms of PPZ. Methods. The solvent emulsification-evaporation method was utilized to form SLNs by using soybean lecithin, glycerol monostearate (GMS), and Tween 80. Statistical optimization was done by the Box-Behnken design method to achieve formulation with optimized particle size, entrapment efficiency, and zeta potential. Also, transmission electron microscopy, in vitro release behavior, differential scanning calorimetry (DSC), and powder X-ray diffractometry (P-XRD) studies and cytotoxicity studies were assessed. Results. Optimization exhibited the significant effect of various excipients on SLN characteristics. Our finding indicated that the mean particle size, zeta potential, and entrapment efficiency of optimized PPZ-SLN were, respectively, 104 ± 3.92 nm , − 28 ± 2.28 mV , and 83 % ± 1.29 . Drug release of PPZ-SLN was observed to be greater than 90% for 48 h that emphasized a sustained-release pattern. The DSC and P-XRD studies revealed the amorphous state of PPZ-SLN. FTIR spectra showed no incompatibility between the drug and the lipid. Performing cytotoxicity studies indicated no significant cytotoxicity on HT-29 cell culture. Conclusion. Our study suggests that PPZ-SLNs can make a promising vehicle for a suitable therapy of schizophrenia for the oral drug delivery system.

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Section: Introductionmentioning

confidence: 99%

Development of Perphenazine-Loaded Solid Lipid Nanoparticles: Statistical Optimization and Cytotoxicity Studies

Farsani

Mahjub

Mohammadi

et al. 2021

BioMed Research International

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“…Different techniques have been investigated in order to improve the solubility of poorly soluble drugs e.g. solubilization in surfactant system [ 7 , 8 ], complexation [ 8 ], micronization [ 1 ], drug derivatization [ 9 ], solid dispersion [ 1 – 6 ], cosolvent technique [ 10 ], nanoparticles [ 11 ], nanoemulsions/self-nanoemulsifying drug delivery systems [ 12 – 14 ] and co-crystal technology etc. [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Influence of the microwave technology on solid dispersions of mefenamic acid and flufenamic acid

et al. 2017

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The present studies were undertaken to develop solvent-free solid dispersions (SDs) for poorly soluble anti-inflammatory drugs mefenamic acid (MA) and flufenamic acid (FFA) in order to enhance their in vitro dissolution rate and in vivo anti-inflammatory effects. The SDs of MA and FFA were prepared using microwaves irradiation (MW) technique. Different carriers such as Pluronic F127® (PL), Eudragit EPO® (EPO), polyethylene glycol 4000 (PEG 4000) and Gelucire 50/13 (GLU) were used for the preparation of SDs. Prepared MW irradiated SDs were characterized physicochemically using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier transform infra-red (FT-IR) spectroscopy, powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM). The physicochemical characteristics and drug release profile of SDs were compared with pure drugs. The results of DSC, TGA, FT-IR, PXRD and SEM showed that SDs were successfully prepared. In vitro dissolution rate of MA and FFA was remarkably enhanced by SDs in comparison with pure MA and FFA. The SDs of MA and FFA prepared using PEG 400 showed higher drug release profile in comparison with those prepared using PL, EPO or GLU. The dissolution efficiency for MA-PEG SD and FFA-PEG SD was obtained as 61.40 and 59.18%, respectively. Optimized SDs were also evaluated for in vivo anti-inflammatory effects in male Wistar rats. The results showed significant % inhibition by MA-PEG (87.74% after 4 h) and FFA-PEG SDs (81.76% after 4 h) in comparison with pure MA (68.09% after 4 h) and pure FFA (55.27% after 4 h) (P<0.05). These results suggested that MW irradiated SDs of MA and FFA could be successfully used for the enhancement of in vitro dissolution rate and in vivo therapeutic efficacy of both drugs.

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“…The amorphous drug formulation [7,33] has demonstrated its capability in drug ol bili enhancemen . The Spring and Parach e effec i he main mechani m of the bioavailability enhancement for amorphous drug formulations [1,6,51]. The intrinsic high level of free energy present in the amorphous form gran he pring effec , a a e here he hermod namic ol bili ( per a ra ion) can be e eral times the saturated concentration of the high active pharmaceutical ingredient [6].…”

Section: Using Amorphous Drug Formulations To Increase Drug Solubilitymentioning

confidence: 99%

“…In our lab, various metastable amorphous electrostatic complexations with high payload, fast dissolution and prolonged high-level supersaturation [1,32,33,35,36] are prepared using the quick, simple, and effective self-assembly drug-polysaccharide complexation method, which only involves the mixing of the drug solution and polymer solution under ambient conditions [33,35,36]. Wean Sin Cheow et al [33] prepared the ionized drug-polyelectrolyte nanoplex for the first time in 2012.…”

Section: Amorphous Drug-electrolyte Nanoparticle Complexmentioning

confidence: 99%

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Amorphous drug-polyelectrolyte nanoparticle complex with controlled release functionality, enhanced amorphous stability, and its continuous production platform

Dong¹

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In spite of various contemporary medicinal approaches developed, there are still more than 40% of drugs in the pharmaceutic market and more than 70% of the drug candidates are insoluble in water, resulting in low oral bioavailability and low therapeutic effectivity of the drugs or drug candidates. Solubility enhancement remains a significant challenge in drug formulation technology development. Various methods have been applied to increase the solubility of poorly soluble drugs.Rendering of drugs into their amorphous form is a promising strategy to enhance the rate and extent of the dissolution of poorly soluble drugs. Nanoization has been used as an effective method to prepare the drug formulations aimed at increasing drug solubility as well. However, most of the existing formulations of poorly soluble drugs are not able to provide fast dissolution or not able to provide the high drug loading required to decrease the pill burden. Amorphous drug-polysaccharide nanoplex with high drug loading (above 80 %) were prepared by the self-assembly electrostatic driven complexation between ionized drug molecules and oppositely charged polysaccharide.

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Amorphous nanoparticle complex of perphenazine and dextran sulfate as a new solubility enhancement strategy of antipsychotic perphenazine

Abstract: The simple yet efficient preparation, excellent physical characteristics, fast dissolution, and high apparent solubility exhibited by the PPZ-DXT nanoplex established its potential as a new bioavailability enhancement strategy of PPZ.

Cited by 18 publications

References 22 publications

Development of Perphenazine-Loaded Solid Lipid Nanoparticles: Statistical Optimization and Cytotoxicity Studies

Development of Perphenazine-Loaded Solid Lipid Nanoparticles: Statistical Optimization and Cytotoxicity Studies

Influence of the microwave technology on solid dispersions of mefenamic acid and flufenamic acid

Amorphous drug-polyelectrolyte nanoparticle complex with controlled release functionality, enhanced amorphous stability, and its continuous production platform

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