Figure - uploaded by Teófilo Cardoso Vasconcelos
Content may be subject to copyright.
Source publication
The increasing number of new chemical entities is bringing new challenges to the field of drug delivery. These drugs present bioavailability issues that are frequently associated with intestinal metabolism or efflux mechanisms. Some excipients, particularly surfactants, have demonstrated a capacity to interfere with these mechanisms, improving drug...
Contexts in source publication
Context 1
... also presented potential to inhibit this mechanism, with decreasing order: Tween20 > Kolliphor EL > Kolliphor RH > PEG400 > Tween80 > Kolliphor H15 [46]. Table 2 presents a summary of the excipients i nteraction with the metabolization systems. ...Context 2
... class II and III excipients present a high risk, particularly when used with drugs that undergo intes tinal metabolization or are efflux subtracts, respec tively. Excipients known to belong to these classes are presented in Tables 2 and 3. These excipients should not be replaced by technologically similar ones with out further studies. ...Citations
... Te aim was to select appropriate polymers for the IBP amorphous solid dispersion (ASD) system. Soluplus ® , Kolliphor ® P188, and Kolliphor ® P407 are frequently employed as carriers with amphiphilic characteristics to improve the solubility of poorly soluble drugs due to their biocompatibility and widespread availability in the commercial market [35][36][37]. As shown in Figure 1, the aqueous solubility of IBP increased as the polymer concentration increased. ...
This study aims to improve the biopharmaceutical, mechanical, and tableting properties of a poorly soluble drug, ibuprofen (IBP), by preparing amorphous solid dispersion (ASD) followed by a sustained-release tablet formulation. A suitable polymer to develop an ASD system was chosen by utilizing the apparent solubility of IBP in various polymer solutions. ASDs containing various ratios of IBP and selected polymer were prepared by the melt fusion (MF) method. ASD containing optimized drug-polymer ratio prepared by freeze-drying (FD) method was characterized and compared physicochemically. The solubility of IBP in water increased 28-fold and 35-fold when formulated as ASD by MF and FD, respectively. Precise formulations showed amorphization of IBP and increased surface area, improving solubility. The dissolution pattern of optimized ASD-IBP in pH 6.8 phosphate buffer after 60 min in MF and FD was enhanced 3-fold. In addition, direct compression tablets comprising optimized ASD granules from MF and FD were made and assessed using compendial and noncompendial methods. ASD-IBP/MF and ASD-IBP/FD formulations showed a similar drug release profile. In addition, 12 h of sustained IBP release from the ASD-IBP-containing tablets was obtained in a phosphate buffer with a pH of 6.8. From the dissolution kinetics analysis, the Weibull model fitted well. The drug release pattern indicated minimal variations between tablets formed using ASD-IBP prepared by both procedures; however, pre- and postcompression assessment parameters differed. From these findings, the application of ASD and sustained-release polymers in matrix formation might be beneficial in improving the solubility and absorption of poorly soluble drugs such as IBP.
... to choose appropriate polymers for the sMsD system for tQM, the apparent solubility of tQM in water was studied in numerous concentrations of pre-dissolved polymers, including soluplus ® , Kolliphor ® P188, and Kolliphor ® P407. soluplus ® , Kolliphor ® P188, and Kolliphor ® P407 are frequently used as pharmaceutical excipients with amphiphilic properties to improve the solubility of poorly water-soluble medications due to their commercial availability and biocompatibility (Vasconcelos et al., 2017;Gangarde et al., 2020;ilie et al., 2021). Due to interactions between lipophilic units of amphiphilic polymers and weakly water-soluble medicines, poorly soluble pharmaceuticals can become more soluble through encapsulation. ...
The present study was designed to develop a self-micellizing solid dispersion (SMSD) containing Thymoquinone (TQM), a phytonutrient obtained from Nigella sativa seeds, aiming to improve its biopharmaceutical and nephroprotective functions. The apparent solubility of TQM in polymer solutions was used to choose an appropriate amphiphilic polymer that could be used to make an SMSD system. Based on the apparent solubility, Soluplus® was selected as an appropriate carrier, and mixing with TQM, SMSD-TQM with different loadings of TQM (5–15%) was made by solvent evaporation and freeze-drying techniques, respectively, and the formulations were optimized. The optimized SMSD-TQM was evaluated in terms of particle size distribution, morphology, release characteristics, pharmacokinetic behavior, and nephroprotective effects in a rat model of acute kidney injury. SMSD-TQM significantly improved the dissolution characteristics (97.8%) of TQM in water within 60 min. Oral administration of SMSD-TQM in rats exhibited a 4.9-fold higher systemic exposure than crystalline TQM. In a cisplatin-induced (6 mg/kg, i.p.) acute kidney-damaged rat model, oral SMSD-TQM (10 mg/kg) improved the nephroprotective effects of TQM based on the results of kidney biomarkers and histological abnormalities. These findings suggest that SMSD-TQM might be efficacious in enhancing the nephroprotective effect of TQM by overcoming biopharmaceutical limitations.
... Esto es un método alternativo para obtener una predicción de la biodisponibilidad in vivo para las cuatro clases, y es útil especialmente para incrementar el número de fármacos clase 1 aptos para una exención de estudios de biodisponibilidad y bioequivalencia in vivo [16]. En 2017 Vasconcelos et al. estudiaron la capacidad de los excipientes de actuar como potenciadores de la permeabilidad y propusieron un Sistema de Clasificación Biofarmacéutica de Excipientes (BCSE, por sus siglas en inglés, Biopharmaceutical Classification System of Excipients) [17]. La Figura 1 muestra la propuesta del BCS con la información complementaria de estos autores. ...
... Sistema de Clasificación Biofarmacéutica de Amidon et al. (7) modificada con información complementaria según lo propuesto por Wu y Benet (14) y Vasconcelos et al.[17]. ...
Resumen Introducción: los fármacos clase II representan un alto porcentaje de las molé-culas en fase de investigación biomédica. Este grupo atrajo la investigación en los últimos años, ya que su baja solubilidad acuosa condiciona su absorción in vivo, lo que plantea un reto para la tecnología farmacéutica. El diseño de dispersiones sólidas (SD) es una técnica que ha tenido éxito y se basa en la dispersión del fármaco en un acarreador polimérico, promoviendo el estado amorfo del primero. Uno de los métodos de obtención de SD es el de fusión, que se puede llevar a cabo en equipos sofisticados, pero los mezcladores de alto corte (HSM) también son una alternativa para obtener granulados por fusión. Objetivo: el objetivo de este trabajo es revisar si han sido reportados procesos de granulación por fusión utilizado HSM para la fabricación de SD y analizar las fortalezas, debilidades, oportunidades y amenazas de este equipo en dicho proceso. Método: en una metodología de revisión documental, se preseleccionaron 90 publicaciones de las bases de datos PubMed, ScienceDirect y Google Scholar de los últimos 20 años, de las cuales ocho describen el uso del método de granulación por fusión en HSM. Resultados: como resultados se vio que el 100% de estos casos reportó mayor solubilidad y velocidad de disolución que el fármaco puro. Se concluye que las empresas locales que cuentan con HSM tienen el potencial Artículo de revisión / https://doi.org/10.15446/rcciquifa.v52n1.102588 Dispersiones sólidas de solubilidad mejorada fabricadas en mezcladores de alto corte 115 para poner en marcha procesos de fabricación de SD exitosos en HSM, con la ventaja de no hacer una inversión adicional. Palabras clave: Dispersiones sólidas, granulación por fusión, mezclador de alto corte, solubilidad, tecnología farmacéutica, SCB clase II. Summary Solid dispersions with improved solubility manufactured in high shear mixers: an opportunity for the local Mexican pharmaceutical industry Introduction: class II drugs represent a high percentage of the molecules in the biomedical research phase. This group has attracted research in recent years, since its low aqueous solubility conditions its absorption in vivo, which poses a challenge for pharmaceutical technology. Solid dispersion design (SD) is a technique that has been successful and is based on the dispersion of the drug in a polymeric carrier, promoting the amorphous state of the former. One of the methods of obtaining SD is melting, which can be carried out in sophisticated equipment, but high shear mixers (HSM) are also an alternative to obtain granules by melting. Aim: the objective of this work is to review if melt granulation processes have been reported using HSM for the manufacture of SD and to analyze the strengths, weaknesses, opportunities and threats of this equipment in said process. Method: in a documentary review methodology, 90 publications from the PubMed, ScienceDirect and Google Scholar databases from the last 20 years were pre-selected, of which eight describe the use of the fusion granulation method in HSM. Results: as results, it was seen that 100% of these cases reported higher solubility and dissolution speed than the pure drug. It is concluded that local companies that have HSM have the potential to launch successful SD manufacturing processes in HSM, with the advantage of not making an additional investment.
... The apparent solubility of DMP in water was tested in the presence of several concentrations of pre-dissolved polymers such as αtocopheryl polyethylene glycol 1,000 succinate (TPGS), Soluplus ® , Kolliphor ® P188, and Kolliphor ® P407 ranging from 2 to 25 mg/mL in the present study for the selection of suitable polymers in the MMSD system for DMP. Because of their commercial availability and biocompatibility; TPGS, Soluplus ® , Kolliphor ® P188, and Kolliphor ® P407 are commonly utilized as pharmaceutical excipients with amphiphilic characteristics to increase the solubility of poorly water-soluble medicines [25][26][27]. As shown in Figure 1, a rise in the aqueous solubility of DMP was detected when the polymer concentration increased. ...
How to cite this article: Halder S, Azad MAK, Islam MS, Hossain I, Shuma ML, Kabir ER. Strategic application of a mixed polymeric micellar solid dispersion system to domperidone for ımproved biopharmaceutical characteristics. J Res Pharm. 2023; 27(2): 860-872. ABSTRACT: The main objective of this work was to improve the biopharmaceutical properties of Domperidone (DMP)-loaded mixed polymeric micellar solid dispersion (MMSD). The apparent solubility of DMP in polymer solutions was used to choose suitable amphiphilic polymers for the preparation of an MMSD system. Different ratios of Soluplus ® and Kolliphor ® P188 (ranging 0-80 %w/w) have been used to prepare the MMSD-DMP by solvent evaporation method and physicochemically characterized. Among the tested different ratios of Soluplus ® and Kolliphor ® P188, the optimal ratio of polymers was selected based on the solubility and surface properties. The solubility of optimized MMSD-DMP in water was found more than 17 times higher compared to that of the crystalline DMP. The crystallinity evaluations of the optimized formulation revealed amorphization of DMP, resulting in enhanced solubility. The drug release pattern did not change significantly between formulations of MMSD-DMP produced by rotary vacuum drying and freeze drying. From these findings, MMSD approach might be a promising dosage option for DMP, offering enhanced biopharmaceutical behaviors leading to improved oral absorption.
... The apparent solubility of TQM in water was tested in several concentrations of predissolved polymers such as Soluplus ® , Kolliphor ® P188, and Kolliphor ® P407 ranging from 5 to 25 mg/mL in the present study for the selection of suitable polymers in the SMSD system for TQM. Because of their commercial availability and biocompatibility, Soluplus ® , Kolliphor ® P188, and Kolliphor ® P407 are commonly utilized as pharmaceutical excipients with amphiphilic characteristics to increase the solubility of poorly water-soluble medicines [42][43][44]. Poorly water-soluble drugs can become more soluble through encapsulation owing to interactions between lipophilic units of amphiphilic polymers and poorly water-soluble drugs. These interactions can lead to the development of polymeric micelles with a hydrophobic core and a hydrophilic shell [45] . ...
The present study was designed to develop a self-micellizing solid dispersion (SMSD) containing Thymoquinone (TQM), a phytonutrient obtained from Nigella sativa seeds, aiming to improve its biopharmaceutical and nephroprotective functions. The apparent solubility of TQM in polymer solutions was used to choose an appropriate amphiphilic polymer that could be used to make an SMSD system. Based on the apparent solubility, Soluplus® was chosen as an appropriate carrier, and mixing with TQM, SMSD-TQM with different loadings of TQM (5–15%) was made by solvent evaporation and freeze-drying techniques, respectively, and the formulations were optimized. The optimized SMSD-TQM was evaluated in terms of particle size distribution, morphology, release characteristics, pharmacokinetic behavior, and nephroprotective effects in a rat model of acute kidney injury. SMSD-TQM significantly improved the dissolution characteristics (97.8%) of TQM in water within 60 min. Oral administration of SMSD-TQM in rats exhibited a 4.9-fold higher systemic exposure than crystalline TQM. In a cisplatin-induced (6 mg/kg, i.p.) acute kidney-damaged rat model, oral SMSD-TQM (10 mg/kg) improved the nephroprotective effects of TQM based on the results of kidney biomarkers and histological abnormalities. These findings suggest that SMSD-TQM might be efficacious in enhancing the nephroprotective effect of TQM by overcoming biopharmaceutical limitations.
... The apparent solubility of DMP in water was tested in the presence of several concentrations of pre-dissolved polymers such as αtocopheryl polyethylene glycol 1,000 succinate (TPGS), Soluplus ® , Kolliphor ® P188, and Kolliphor ® P407 ranging from 2 to 25 mg/mL in the present study for the selection of suitable polymers in the MMSD system for DMP. Because of their commercial availability and biocompatibility; TPGS, Soluplus ® , Kolliphor ® P188, and Kolliphor ® P407 are commonly utilized as pharmaceutical excipients with amphiphilic characteristics to increase the solubility of poorly water-soluble medicines [25][26][27]. As shown in Figure 1, a rise in the aqueous solubility of DMP was detected when the polymer concentration increased. ...
... The components used in the formulation of SEDDS can facilitate the solubilization of FEX, favoring its absorption, since these systems make the drug available in nanodroplets offering a high surface area for absorption (Date et al., 2010). Behyond this, the surfactants have been found to enhance the absorption of compounds by both transcellular and paracellular routes through reduction of the membrane viscosity and increasing its elasticity (Vasconcelos et al., 2017). In addition, we prepared formulations with pegylated surfactants (Polyborbate 80 and PEG-40 Hydrogenated Castor Oil) and the presence of these surfactants provides a PEG-based hydrophilic coating to the nanocarrier, contributing to increase its permeation properties across mucus and, consequently, the systemic delivery of FEXI (Haddadzadegan et al. 2022). ...
The aim of this study was to develop, characterize and evaluate the in vivo oral efficacy of self-emulsifying drug delivery systems (SEDDS) containing fexinidazole (FEX) in the experimental treatment of visceral leishmaniasis (VL). The developed FEX-SEDDS formulation presented as a clear, yellowish liquid, with absence of precipitate. The droplet size, polydispersion index and zeta potential after dilution in water (1:200) was of 91 ± 3 nm, 0.242 ± 0.005 and -16.7 ± 0.2, respectively. In the simulated gastric and intestinal media, the FEX-SEDDS had a size of 97 ± 1 and 106 ± 9 nm, respectively. The FEX retention in droplet after SEDDS dilution in simulated gastrointestinal media was almost 100%. Antileishmanial efficacy studies showed that FEX-SEDDS was the only treatment able to significantly (p <0.05) reduce the parasite burden in the liver and spleen of animals experimentally infected with Leishmania infantum. Our intestinal permeability data suggest that FEX-SEDDS showed no evidence of injury to the intestinal mucosa. These findings suggest that FEX-SEDDS can be a promising oral alternative for the treatment of VL caused by L. infantum.
... Perkembangan farmasi modern telah melaporkan bahwa eksipien hanya berkontribusi terhadap sifat formulasi sediaan, seperti meningkatkan kelarutan obat dan meningkatkan manufakturabilitas. Akan tetapi, semakin banyak bukti menunjukkan bahwa eksipien dapat mempengaruhi farmakokinetik bahan aktif farmasi melalui berbagai mekanisme pada proses absorbsi, distribusi, metabolisme, dan eliminasi [3,5,6,7,8,9,10]. Selain itu, banyak penelitian menyatakan bahwa sejumlah eksipien menimbulkan efek biologis yang dapat mengubah hasil pengobatan [11,12,13,14]. ...
Penentuan bioavailabilitas suatu obat menjadi parameter penting untuk mengetahui jumlah serta kecepatan obat diabsropsi dalam tubuh. Diketahui bahwa pria dan wanita memiliki respon yang berbeda dalam menerima obat, selain itu perbedaan perilaku obat juga disebabkan oleh variabilitas antar individu. Dalam pembuatan produk obat, bahan aktif farmasi secara rutin diformulasikan dengan berbagai eksipien, oleh karena itu penentuan eksipien juga merupakan parameter kritis dalam suatu produk obat. Review artikel ini bertujuan untuk memuat bukti mengenai hubungan jenis kelamin terhadap pengaruh eksipien farmasi pada transporter P-glikoprotein (P-gp) dalam mempengaruhi bioavailabilitas obat. Sebanyak 54 artikel selama sepuluh tahun terakhir diperoleh secara elektronik melalui situs PubMed dan Google Scholar. Hasil studi ini menunjukkan peningkatan bioavailabilitas obat dengan traspoerter P-gp hanya terjadi pada subjek tikus jantan dan atau subjek manusia pria. Hal tersebut dikarenakan protein dan kelimpahan mRNA yang lebih tinggi pada jaringan usus kecil pria bila dibandingkan dengan wanita di lokasi yang sama. Dengan demikian, studi ini harus dipertimbangkan secara hati-hati terhadap ko-formulasi eksipien farmasi dengan obat-obatan yang merupakan substrat P-gp.
... Pharmaceutical dosage formulations usually contain both pharmacologically active compounds and excipients to produce proper formulations for patients [1][2][3]. Although most pharmaceutical excipients (PEs) are inactive, they are critical and essential components in finished pharmaceutical products, and they can be used as binders, disintegrants, and surfactants, etc. [4]. For example, surfactants are used to solubilize hydrophobic drugs, methylcellulose can be used to prepare drug suspensions or added to tablets as a disintegrating agent, and cyclodextrin can be used to improve drug stability or control drug release [5]. ...
Pharmaceutical excipients (PEs) are substances included in drug formulations. Recent studies have revealed that some PEs can affect the activity of metabolic enzymes and drug transporters; however, the effects of PEs on CYP2C8 and its interaction potential with drugs remain unclear. In this study, we evaluated the effects of Tween 80 and EL−35 on CYP2C8 in vitro and further investigated their impacts on the PK of paclitaxel (PTX) in rats after single or multiple doses. The in vitro study indicated that Tween 80 and EL−35 inhibited CYP2C8 activity in human and rat liver microsomes. EL−35 also decreased the expression of CYP2C8 in HepG2 cells. In the in vivo study, Tween 80 did not alter the PK of PTX after single or multiple doses, whereas EL−35 administered for 14 days significantly increased the AUC and MRT of PTX. Further analysis indicated that multiple-dose EL−35 reduced the expression of Cyp2c22 and production of 6-OH-PTX in the rat liver. Our study suggested that short-term exposure to both PEs did not affect the PK of PTX in rats, but multiple doses of EL−35 increased the AUC and MRT of PTX by downregulating the hepatic expression of Cyp2c22. Such effects should be taken into consideration during drug formulation and administration.
... Furthermore, the ability to boost drug stability by inhibiting CYP3A4 and CYP2C9-mediated metabolism was confirmed by TPGS [80]. TPGS has shown little inhibition effect on CYP3A activity in other studies [81], which may be linked to dosage [82]. Nanocrystals, nanosuspensions, the self-emulsifying/micro emulsifying drug delivery mechanism (SEDDS/SMEDDS), solid dispersions/tablet, solid lipid nanoparticles (SLNs), liposomes and micelles and emulsified TPGS nanoparticles are included in the TPGS formulations. ...
D-tocopheryl polyethylene glycol succinate (Vitamin E TPGS) has been approved as a safe pharmaceutical adjuvant by FDA, and several drug delivery systems (DDS) based on TPGS have been developed. TPGS properties as a P-gp inhibitor, solubilizer/absorption and permeation enhancer in drug delivery and TPGS-related formulations such as nanocrystals, nanosuspensions, tablets/solid dispersions, vaccine system adjuvant, nutritional supplement, film plasticizer, anticancer reagent, and so on, are discussed in this review. Consequenly, TPGS can inhibit ATP-dependent P-glycoprotein activity and act as a potent excipient that promotes the efficiency of delivery and the therapeutic effect of drugs. Inhibition of P-gp occurs through mitochondria-dependent inhibition of the P-gp pump. Many of the latest studies address the use of TPGS for many poorly water-soluble or permeable drugs in the manufacture of nanodrugs or other formulations. In addition, it has been reported that TPGS shows a robust improvement in chylomicron secretion at low concentrations and improves intestinal lymphatic transport, which would also boost the potential of drug absorption. It also indicates that there are still many problems facing clinical translation of TPGS-based nanomedicines, requiring a more deep evaluation of TPGS properties and a future-based delivery method.
