Hyperthermia-Induced In Situ Drug Amorphization by Superparamagnetic Nanoparticles in Oral Dosage Forms

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Hyperthermia-Induced In Situ Drug Amorphization by Superparamagnetic Nanoparticles in Oral Dosage Forms

Ansari, Shaquib Rahman, 1993- (författare): Uppsala universitet,Institutionen för farmaci,Science for Life Laboratory, SciLifeLab

Hempel, Nele-Johanna (författare): Univ Copenhagen, Dept Pharm, DK-2100 Copenhagen, Denmark.;Novo Nordisk AS, Global Res Technol, Novo Nordisk Pk 1, DK-2760 Malov, Denmark.

Asad, Shno (författare): Uppsala universitet,Institutionen för farmaci,Science for Life Laboratory, SciLifeLab

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Svedlindh, Peter (författare): Uppsala universitet,Fasta tillståndets fysik

Bergström, Christel A. S., 1973- (författare): Uppsala universitet,Institutionen för farmaci,The Swedish Drug Delivery Center

Löbmann, Korbinian (författare): Univ Copenhagen, Dept Pharm, DK-2100 Copenhagen, Denmark.

Teleki, Alexandra (författare): Uppsala universitet,Institutionen för farmaci,Science for Life Laboratory, SciLifeLab

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2022-04-22
2022
Engelska.
Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 14:19, s. 21978-21988

Relaterad länk:: https://doi.org/10.1...; visa fler...; https://uu.diva-port... (primary) (Raw object); https://urn.kb.se/re...; https://doi.org/10.1...; visa färre...

Tidskriftsartikel (refereegranskat)

Abstract Ämnesord

Stäng

Superparamagnetic iron oxide nanoparticles (SPIONs) generate heat upon exposure to an alternating magnetic field (AMF), which has been studied for hyperthermia treatment and triggered drug release. This study introduces a novel application of magnetic hyperthermia to induce amorphization of a poorly aqueous soluble drug, celecoxib, in situ in tablets for oral administration. Poor aqueous solubility of many drug candidates is a major hurdle in oral drug development. A novel approach to overcome this challenge is in situ amorphization of crystalline drugs. This method facilitates amorphization by molecular dispersion of the drug in a polymeric network inside a tablet, circumventing the physical instability encountered during the manufacturing and storage of conventional amorphous solid dispersions. However, the current shortcomings of this approach include low drug loading, toxicity of excipients, and drug degradation. Here, doped SPIONs produced by flame spray pyrolysis are compacted with polyvinylpyrrolidone and celecoxib and exposed to an AMF in solid state. A design of experiments approach was used to investigate the effects of SPION composition (Zn0.5Fe2.5O4 and Mn0.5Fe2.5O4), doped SPION content (10–20 wt %), drug load (30–50 wt %), and duration of AMF (3–15 min) on the degree of drug amorphization. The degree of amorphization is strongly linked to the maximum tablet temperature achieved during the AMF exposure (r = 0.96), which depends on the SPION composition and content in the tablets. Complete amorphization is achieved with 20 wt % Mn0.5Fe2.5O4 and 30 wt % celecoxib in the tablets that reached the maximum temperature of 165.2 °C after 15 min of AMF exposure. Furthermore, manganese ferrite exhibits no toxicity in human intestinal Caco-2 cell lines. The resulting maximum solubility of in situ amorphized celecoxib is 5 times higher than that of crystalline celecoxib in biorelevant intestinal fluid. This demonstrates the promising capability of SPIONs as enabling excipients to magnetically induce amorphization in situ in oral dosage forms.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
NATURVETENSKAP -- Kemi -- Materialkemi (hsv//swe)
NATURAL SCIENCES -- Chemical Sciences -- Materials Chemistry (hsv//eng)

Nyckelord

superparamagnetic nanoparticles
oral drug delivery
in situ drug amorphization
amorphous solid dispersions
magnetic hyperthermia

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Av författaren/redakt...: Ansari, Shaquib ...; Hempel, Nele-Joh ...; Asad, Shno; Svedlindh, Peter; Bergström, Chris ...; Löbmann, Korbini ...; visa fler...; Teleki, Alexandr ...; visa färre...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Farmaceutiska ve ...

NATURVETENSKAP: NATURVETENSKAP; och Kemi; och Materialkemi

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Av lärosätet: Uppsala universitet

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