Povacoat affecting solid-state polymorphic changes of indomethacin after co-evaporation from different types of solvents via conventional and microwave drying techniques

Lin, Shan‐Yang; Lin, Hong-Liang; Chi, Ying-Ting; Hung, Ru-Ying; Huang, Yu-Ting; Kao, Chi-Yu; Hsieh, Wei-Hsien

doi:10.1016/j.ajps.2015.09.005

Cited by 6 publications

(4 citation statements)

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“…The broad endothermic event observed in the DSC and TG curves of Povacoat TM (Figures 5.6 and 5.7) was assigned to the moisture content. This broad peak may also have contributed to the glass transition event, as previously reported, at 82°C (311). Furthermore, as confirmed by XRPD (Figure 5.8), this polymer is completely amorphous.…”

Section: Discussionsupporting

confidence: 79%

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Erding formula and bioactive markers in hyperuricemia: towards rational scientific approaches for the modernization of Traditional Chinese Medicine

Zuo¹

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Introduction: Traditional Chinese Medicine (TCM) represents one of the first holistic approaches in the world to treat and prevent disease. Herbal medicine is one of the major therapeutic remedy in TCM. It often involves multi-herb therapies instead of single herb preparations. Parallel to western medicine, hundreds of herbal formulas have been made available as finished products. Currently, the use of herbal products is popular as treatment option or to complement western medicine. Indications of the herbal formulas were established by TCM terms such as "heat-clearing and/or detoxifying" which lack modern pharmacological meanings. It is difficult for people without relevant background to understand such terms and their implications for treatments. Furthermore, due to the quality control issues of herbal medicines which contain multiple constituents, consumers may be confronted with the risk of using unstandardized products. Hence, in this thesis, the modernization of TCM is discussed through employing scientific pharmaceutical approaches to a traditional formula, called Erding formula (EF). The aim was to investigate if a new indication, hyperuricemia, can be assigned to a heat-clearing and detoxifying formula. Our hypothesis was: Can Erding formula be used for hyperuricemia treatment and is esculetin a bioactive marker for this new indication? Methods: A hypoxanthine and potassium oxonate-induced hyperuricemic mouse model, a xylene-induced inflammatory mouse model, and an acetic acid-induced pain model were used to investigate EF and its constituent herbs. The quantity of esculetin was measured by ` ii high-performance liquid chromatography. The therapeutic effect of esculetin was assessed using potassium oxonate induced hyperuricemic mouse model, and esculetin and its metabolites were characterized in serum via ultra-performance liquid chromatographyquadrupole time-of-flight mass spectrometry. To develop a modern dosage form, a laboratory-scale wet bead milling approach was employed to prepare esculetin nanocrystals. The formulation was further optimized by design of experiment, and an optimized formulation was then characterized for its saturation solubility and short-term stability.Results: The study showed that EF and Viola yedoensis Makino (Viola) lowered uric acid (UA) levels, while EF and all four individual herbs had anti-inflammatory and analgesic activities. These findings revealed that EF was able to treat hyperuricemia and suggested that Viola was the main herb in EF on reducing UA levels. The study showed that esculetin significantly reduced UA levels and six metabolites of esculetin were identified in serum.This confirms that esculetin was absorbed and is a suitable bioactive and quality control marker for EF in hyperuricemia treatment. An esculetin-Povacoat nanocrystal formulation with a 200 nm particle size was successfully prepared. The formulation presented up to a 1.5-fold increase in saturation solubility compared to the bulk esculetin and it was stable for 180 days. Conclusion:The studies p...

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Section: Discussionsupporting

confidence: 79%

“…Furthermore, as confirmed by XRPD (Figure 5.8), this polymer is completely amorphous. The additional endothermic event between 160 and 211°C was associated with intramolecular ester condensation (cyclic anhydride formation) induced by the heating, as reported by Lin et al (311).…”

Section: Discussionsupporting

confidence: 64%

Erding formula and bioactive markers in hyperuricemia: towards rational scientific approaches for the modernization of Traditional Chinese Medicine

Zuo¹

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“…Developed as a pharmaceutical excipient, Povacoat ® , with consolidated use for coating and wet granulation processes, has a pKa of 3.56 in strong acid and 9.5 in strong base, with a load of 0.03 in pH 6.5. This copolymer is established as a stabilizing agent for obtaining nanocrystals, preventing aggregations, and improving the saturation solubility of nanosuspensions with drugs with nanometer-scale particles [ 28 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ].…”

Section: Resultsmentioning

confidence: 99%

Besifloxacin Nanocrystal: Towards an Innovative Ophthalmic Preparation

et al. 2022

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Bacterial conjunctivitis significantly impacts public health, including more than one-third of eye diseases reported worldwide. It is an infection caused by various aerobic and anaerobic bacteria and is highly contagious. Therefore, it has a high incidence of bacterial resistance to the antibiotics commonly used for treatment. Among the most recent antibiotics, besifloxacin is a fourth-generation fluoroquinolone antibiotic indicated exclusively for topical ophthalmic use. Due to its importance in treating bacterial conjunctivitis and its low solubility in water, limiting its efficacy, a nanotechnology-based drug delivery preparation was developed to overcome this hurdle. Besifloxacin nanocrystals were prepared by small-scale wet milling and response surface methodology, using Povacoat® as a stabilizer. The particle’s average hydrodynamic diameter (Z-ave) was approximately 550 nm (17 times smaller than raw material), with a polydispersity index (PdI) of less than 0.2. The saturation solubility increased about two times compared to the raw material, making it possible to increase the dissolution rate of this drug substance, potentially improving its bioavailability and safety. The optimized preparation was stable under an accelerated stability study (90 days). The Z-ave, PZ, PdI, and content did not alter significantly during this period. Furthermore, the 0.6% m/m besifloxacin nanocrystals at the maximum dose and the Povacoat® stabilizer did not show toxicity in Galleria mellonella larvae. The innovative ophthalmic preparation minimum inhibitory concentration (MIC) was 0.0960 µg/mL and 1.60 µg/mL against Staphylococcus aureus and Pseudomonas aeruginosa, respectively, confirming in vitro efficacy. Therefore, besifloxacin nanocrystals revealed the potential for reduced dosing of the drug substance, with a minor occurrence of adverse effects and greater patient adherence to treatment.

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“…Desenvolvido como excipiente farmacêutico, com utilização já consolidada para processos de revestimentos e de granulação úmida, o Povacoat ® (Figura 14) tem pKa de 3,56 em ácido forte e 9,5 em base forte, com carga de 0,03 em pH 6,5. Esse copolímero vem sendo estabelecido como agente estabilizante, prevenindo agregações de nanocristais (COMPRI, et al, 2019;LIN, et al, 2016;MELO, et al 2020;OCHI, et al, 2014;UEDA, et al, 2014;YUMINOKI, et al, 2014;YUMINOKI, et al, 2016;ZUO, et al, 2020). Para evitar alterações do tamanho, do índice de polidispersão e prevenir dissolução dos nanocristais de besifloxacino durante as medições, foi utilizada solução saturada do fármaco para dispersão na técnica DLS e tampão fosfato pH 7,0 para a técnica DL.…”

Section: Estudo Exploratório I: Diâmetro Hidrodinâmico Médio (Dhm) Da...unclassified

Nanocristais de besifloxacino para o tratamento de conjuntivite bacteriana: preparação, caracterização físico-química e toxicidade

Jesus¹

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À minha esposa, com amor e gratidão por sua compreensão, aos meus filhos, à minha família, amigos e colegas por todo apoio e torcida. AGRADECIMENTOSEm primeiro lugar, agradeço a Deus por iluminar e me prover de coragem para realizar esse sonho, Ele que abençoa a minha vida em todas as circunstâncias.Agradeço à Profa. Dra. Nádia Araci Bou Chacra por me aceitar como aluno de pósgraduação, por toda dedicação, aconselhamentos, paciência e confiança.Aos meus colegas de laboratório, por todos ensinamentos, parcerias e discussões técnicas.À toda equipe do Departamento de Farmácia do Programa de Pós-graduação em Fármaco e Medicamentos. À Profa. Dra. Iolanda Midea Cuccovia do Departamento de Bioquímica (IQ/USP) que abriu as portas do seu laboratório, possibilitando a conclusão de etapas essenciais dessse estudo, em tempo adequado. Ao Prof. Dr. Humberto Gomes Ferraz e à toda equipe e colegas do DEINFAR, pelo compartilhamento do laboratório e equipamentos. À Profa. Dra. Kelly Ishida e a doutoranda Thayná L. Barreto, pelos ensinamentos e parceria referente às análises de toxicidade. Ao Prof. Dr. Felipe Rabelo Lourenço pelo apoio na realização das análises microbiológicas. À Profa. Dra. Priscyla Daniely M. Gaspari e ao Prof. Dr. Newton Andréo Filho pelos comentários valiosos durante meu exame de qualificação. Ao Grupo Eurofarma, principalmente, à unidade Momenta e aos meus gestores que me deram flexibilidade para concluir esse projeto. À minha família, colegas e amigos que torceram por mim. Especialmente, a minha esposa pela compreensão e paciência e aos meus filhos Victor e Heloísa que me proporcionam motivação todos os dias.

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Povacoat affecting solid-state polymorphic changes of indomethacin after co-evaporation from different types of solvents via conventional and microwave drying techniques

Cited by 6 publications

References 35 publications

Erding formula and bioactive markers in hyperuricemia: towards rational scientific approaches for the modernization of Traditional Chinese Medicine

Erding formula and bioactive markers in hyperuricemia: towards rational scientific approaches for the modernization of Traditional Chinese Medicine

Besifloxacin Nanocrystal: Towards an Innovative Ophthalmic Preparation

Nanocristais de besifloxacino para o tratamento de conjuntivite bacteriana: preparação, caracterização físico-química e toxicidade

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