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BACKGROUND: Vitamin D3 (VD3) deficiency among children in Saudi Arabia remains a pressing concern due to its poor bioavailability and the limitations of current pediatric formulations. To address this challenge, we developed a groundbreaking pediatric self-nanoemulsifying drug delivery system (Bio-SNEDDS) for VD3, fortified with black seed oil and moringa seed oil for dual therapeutic benefits. Through meticulous formulation optimization using ternary phase diagrams and comprehensive testing, our Bio-SNEDDS demonstrated exceptional performance. METHODS: Bio-SNEDDS were manufactured by incorporating Black seed oil and moringa seed oil as bioactive nutraceutical excipients along with various cosurfactant and surfactants. Bio-SNEDDS were systematically optimized through ternary phase diagrams, visual tests, droplet size analysis, drug solubilization studies, dispersion assessments, and pharmacokinetic testing in rats compared to Vi-De 3®. RESULTS: Pseudoternary phase diagrams identified oil blends producing large nanoemulsion regions optimal for SNEDDS formation. The optimized F1 Bio-SNEDDS showed a mean droplet diameter of 33.7 nm, solubilized 154.46 mg/g VD3 with no metabolite formation, and maintained >88% VD3 in solution during 24 h dispersion testing. Notably, in vivo pharmacokinetic evaluation at a high VD3 dose demonstrated an approximately two-fold greater relative bioavailability over Vi-De 3®, validating the superb oral delivery performance of Bio-SNEDDS even under challenging high-dose conditions. CONCLUSIONS: The Bio-SNEDDS provides an effective VD3 delivery strategy with established in vivo superiority over marketed products, along with offering additional health benefits from the natural oils.
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Sistemas de Liberación de Medicamentos , Nanopartículas , Humanos , Ratas , Animales , Niño , Emulsiones , Solubilidad , Tensoactivos , Aceites de Plantas , Tamaño de la Partícula , Administración Oral , Disponibilidad BiológicaRESUMEN
The COVID-19 pandemic disrupted healthcare worldwide, potentially impacting disease management. The objective of this study was to assess the self-management behaviors of Saudi patients with diabetes during and after the COVID pandemic period using the Arabic version of the Diabetes Self-Management Questionnaire (DSMQ). A cross-sectional study was conducted in patients aged ≥18 years diagnosed with type 2 diabetes mellitus who had at least one ambulatory clinic visit in each of the specified time frames (Pre-COVID-19: 1 January 2019-21 March 2020; COVID-19 Time frame: 22 March 2020 to 30 April 2021) utilizing the DSMQ questionnaire, with an additional three questions specifically related to their diabetes care during the COVID pandemic. A total of 341 patients participated in the study. The study results revealed that the surveyed patients showed moderately high self-care activities post-COVID-19. Total DSMQ scores were significantly higher in patients aged >60 years versus younger groups (p < 0.05). Scores were significantly lower in patients diagnosed for 1-5 years versus longer durations (p < 0.05). Patients on insulin had higher glucose management sub-scores than oral medication users (p < 0.05). Overall, DSMQ scores were higher than the pre-pandemic Saudi population and Turkish post-pandemic findings. DSMQ results suggest that, while COVID-19 negatively impacted some self-management domains, the Saudi patients surveyed in this study upheld relatively good diabetes control during the pandemic. Further research is warranted on specific barriers to optimize diabetes care during public health crises.
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Lansoprazole (LZP) is used to treat acid-related gastrointestinal disorders; however, its low aqueous solubility limits its oral absorption. Black seed oil (BSO) has gastroprotective effects, making it a promising addition to gastric treatment regimens. The present study aims to develop a stable multifunctional formulation integrating solid dispersion (SD) technology with a bioactive self-nanoemulsifying drug delivery system (SNEDDS) based on BSO to synergistically enhance LZP delivery and therapeutic effects. The LZP-loaded SNEDDS was prepared using BSO, Transcutol P, and Kolliphor EL. SDs were produced by microwave irradiation and lyophilization using different polymers. The formulations were characterized by particle apparent hydrodynamic radius analysis, zeta potential, SEM, DSC, PXRD, and in vitro dissolution testing. Their chemical and physical stability under accelerated conditions was also examined. Physicochemical characterization revealed that the dispersed systems were in the nanosize range (<500 nm). DSC and PXRD studies revealed that lyophilization more potently disrupted LZP crystallinity versus microwave heating. The SNEDDS effectively solubilized LZP but degraded completely within 1 day. Lyophilized SDs with Pluronic F-127 demonstrated the highest LZP dissolution efficiency (3.5-fold vs. drug) and maintained chemical stability (>97%) for 1 month. SDs combined with the SNEDDS had variable effects suggesting that the synergistic benefits were dependent on the formulation and preparation method. Lyophilized LZP-Pluronic F127 SD enabled effective and stable LZP delivery alongside the bioactive effects of the BSO-based SNEDDS. This multifunctional system is a promising candidate with the potential for optimized gastrointestinal delivery of LZP and bioactive components.
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Oral anticancer therapy mostly faces the challenges of low aqueous solubility, poor and irregular absorption from the gastrointestinal tract, food-influenced absorption, high first-pass metabolism, non-targeted delivery, and severe systemic and local adverse effects. Interest has been growing in bioactive self-nanoemulsifying drug delivery systems (bio-SNEDDSs) using lipid-based excipients within nanomedicine. This study aimed to develop novel bio-SNEDDS to deliver antiviral remdesivir and baricitinib for the treatment of breast and lung cancers. Pure natural oils used in bio-SNEDDS were analyzed using GC-MS to examine bioactive constituents. The initial evaluation of bio-SNEDDSs were performed based on self-emulsification assessment, particle size analysis, zeta potential, viscosity measurement, and transmission electron microscopy (TEM). The single and combined anticancer effects of remdesivir and baricitinib in different bio-SNEDDS formulations were investigated in MDA-MB-231 (breast cancer) and A549 (lung cancer) cell lines. The results from the GC-MS analysis of bioactive oils BSO and FSO showed pharmacologically active constituents, such as thymoquinone, isoborneol, paeonol and p-cymenene, and squalene, respectively. The representative F5 bio-SNEDDSs showed relatively uniform, nanosized (247 nm) droplet along with acceptable zeta potential values (+29 mV). The viscosity of the F5 bio-SNEDDS was recorded within 0.69 Cp. The TEM suggested uniform spherical droplets upon aqueous dispersions. Drug-free, remdesivir and baricitinib-loaded bio-SNEDDSs (combined) showed superior anticancer effects with IC50 value that ranged from 1.9-4.2 µg/mL (for breast cancer), 2.4-5.8 µg/mL (for lung cancer), and 3.05-5.44 µg/mL (human fibroblasts cell line). In conclusion, the representative F5 bio-SNEDDS could be a promising candidate for improving the anticancer effect of remdesivir and baricitinib along with their existing antiviral performance in combined dosage form.
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Neoplasias de la Mama , Neoplasias Pulmonares , Nanopartículas , Humanos , Femenino , Reposicionamiento de Medicamentos , Administración Oral , Emulsiones , Sistemas de Liberación de Medicamentos/métodos , Solubilidad , Aceites , Tamaño de la Partícula , Disponibilidad Biológica , Tensoactivos , Liberación de FármacosRESUMEN
The polar fractions of the Juniperus species are rich in bioflavonoid contents. Phytochemical study of the polar fraction of Juniperus sabina aerial parts resulted in the isolation of cupressuflavone (CPF) as the major component in addition to another two bioflavonoids, amentoflavone and robustaflavone. Biflavonoids have various biological activities, such as antioxidant, anti-inflammatory, antibacterial, antiviral, hypoglycemic, neuroprotective, and antipsychotic effects. Previous studies have shown that the metabolism and elimination of biflavonoids in rats are fast, and their oral bioavailability is very low. One of the methods to improve the bioavailability of drugs is to alter the route of administration. Recently, nose-to-brain drug delivery has emerged as a reliable method to bypass the blood-brain barrier and treat neurological disorders. To find the most effective CPF formulation for reaching the brain, three different CPF formulations (A, B and C) were prepared as self-emulsifying drug delivery systems (SEDDS). The formulations were administered via the intranasal (IN) route and their effect on the spontaneous motor activity in addition to motor coordination and balance of rats was observed using the activity cage and rotarod, respectively. Moreover, pharmacokinetic investigation was used to determine the blood concentrations of the best formulation after 12 h. of the IN dose. The results showed that formulations B and C, but not A, decreased the locomotor activity and balance of rats. Formula C at IN dose of 5 mg/kg expressed the strongest effect on the tested animals.
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Biflavonoides , Juniperus , Ratas , Animales , Juniperus/química , Biflavonoides/farmacología , Biflavonoides/metabolismo , Solubilidad , Sistemas de Liberación de Medicamentos/métodos , Encéfalo/metabolismo , Administración Intranasal , Actividad Motora , Disponibilidad BiológicaRESUMEN
BACKGROUND: Among lipid-based formulations, self-nanoemulsifying drug delivery systems (SNEDDS) have captured a spotlight, captivating both academia and the pharmaceutical industry. These remarkable formulations offer a valuable option, yet their liquid form presents certain challenges for delivering poorly soluble drugs. Ensuring compatibility with capsule shells, maintaining physical and chemical stability, and understanding their impact on lipolysis remain vital areas of exploration. Therefore, the incorporation of this liquid formulation into a solid dosage form (S-SNEDDS) is compelling and desirable. S-SNEDDSs, prepared by adsorption, enhances formulation stability but retards drug dissolution. This study aims to design drug-free solid S-SNEDDS + solid dispersion (SD) as a novel combination to enhance cinnarizine (CN) stability upon storage while maintaining enhanced drug dissolution. METHODS: Drug-free liquid SNEDDSs were solidified using Neusilin® US2 at a 1:1 ratio. CN-SDs were prepared using freeze-drying technology. The SDs that were developed underwent characterization using various techniques, including scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). In vitro lipolysis studies were conducted to evaluate the effect of the combined system on the performance of the formulation upon exposure to enzymes within biorelevant media. RESULTS: In agreement with the DSC and XRD results, FTIR confirmed the amorphization of CN within the freeze-dried solid dispersion (FD-SD) systems. The in vitro lipolysis studies showed that the drug-free S-SNEDDS + SD combination was able to maintain a significant portion of the initial CN in solution even in the presence of lipase for up to 30 min. The accelerated stability studies showed that the drug-free S-SNEDDS + SD combination maintained 96% intact CN in an amorphous state and more than 90% release at pH 1.2 for up to 6 months, while the dissolution profile at pH 6.8 showed a significant drop in CN release upon storage. CONCLUSIONS: Overall, the developed formulation could be a potential technique to enhance the dissolution of weakly basic drugs that possess challenging stability limitations.
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Sistemas de Liberación de Medicamentos , Nanopartículas , Solubilidad , Emulsiones/química , Sistemas de Liberación de Medicamentos/métodos , Liberación de Fármacos , Microscopía Electrónica de Rastreo , Tamaño de la Partícula , Nanopartículas/químicaRESUMEN
Purpose: Ramipril (RMP)an angiotensin-converting enzyme (ACE) inhibitorand thymoquinone (THQ) suffer from poor oral bioavailability. Developing a combined liquid SNEDDS that comprises RMP and black seed oil (as a natural source of THQ) could lead to several formulations and therapeutic benefits. Methods: The present study involved comprehensive optimization of RMP/THQ liquid SNEDDS using self-emulsification assessment, equilibrium solubility studies, droplet size analysis, and experimentally designed phase diagrams. In addition, the optimized RMP/THQ SNEDDS was evaluated against pure RMP, pure THQ, and the combined pure RMP + RMP-free SNEDDS (capsule-in-capsule) dosage form via in vitro dissolution studies. Results: The phase diagram study revealed that black seed oil (BSO) showed enhanced self-emulsification efficiency with the cosolvent (Transcutol P) and hydrogenated castor oil. The phase diagram studies also revealed that the optimized formulation BSO/TCP/HCO-30 (32.25/27.75/40 % w/w) showed high apparent solubility of RMP (25.5 mg/g), good THQ content (2.7 mg/g), and nanometric (51 nm) droplet size. The in-vitro dissolution studies revealed that the optimized drug-loaded SNEDDS showed good release of RMP and THQ (up to 86% and 89%, respectively). Similarly, the isolation between RMP and SNEDDS (pure RMP + RMP-free SNEDDS) using capsule-in-capsule technology showed >84% RMP release and >82% THQ release. Conclusions: The combined pure RMP + RMP-free SNEDDS (containing black seed oil) could be a potential dosage form combining the solubilization benefits of SNEDDSs, enhancing the release of RMP/THQ along with enhancing RMP stability through its isolation from lipid-based excipients during storage.
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This research demonstrates the use of fused deposition modeling (FDM) 3D printing to control the delivery of multiple drugs containing bioactive self-nano emulsifying drug-delivery systems (SNEDDSs). Around two-thirds of the new chemical entities being introduced in the market are associated with some inherent issues, such as poor solubility and high lipophilicity. SNEDDSs provide for an innovative and easy way to develop a delivery platform for such drugs. Combining this platform with FDM 3D printing would further aid in developing new strategies for delivering poorly soluble drugs and personalized drug-delivery systems with added therapeutic benefits. This study evaluates the performance of a 3D-printed container system containing curcumin (CUR)- and lansoprazole (LNS)-loaded SNEDDS. The SNEDDS showed 50% antioxidant activity (IC50) at concentrations of around 330.1 µg/mL and 393.3 µg/mL in the DPPH and ABTS radical scavenging assay, respectively. These SNEDDSs were loaded with no degradation and leakage from the 3D-printed container. We were able to delay the release of the SNEDDS from the hollow prints while controlling the print wall thickness to achieve lag phases of 30 min and 60 min before the release from the 0.4 mm and 1 mm wall thicknesses, respectively. Combining these two innovative drug-delivery strategies demonstrates a novel option for tackling the problems associated with multi-drug delivery and delivery of drugs susceptible to degradation in, i.e., gastric pH for targeting disease conditions throughout the gastrointestinal tract (GIT). It is also envisaged that such delivery systems reported herein can be an ideal solution to deliver many challenging molecules, such as biologics, orally or near the target site in the future, thus opening a new paradigm for multi-drug-delivery systems.
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BACKGROUND: Solidification by high surface area adsorbents has been associated with major obstacles in drug release. Accordingly, new approaches are highly demanded to solve these limitations. The current study proposes to improve the drug release of solidified self-nanoemulsifying drug delivery systems (SNEDDS) to present dual enhancement of drug solubilization and formulation stabilization, using cinnarizine (CN) as a model drug. METHODS: The solidification process involved the precoating of adsorbent by lyophilization of the aqueous dispersion of polymer-adsorbent mixture using water as a green solvent. Then, the precoated adsorbent was mixed with drug-loaded liquid SNEDDS to prepare solid SNEDDS. The solid-state characterization of developed cured S-SNEDDS was done using X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC). In vitro dissolution studies were conducted to investigate CN SNEDDS performance at pH 1.2 and 6.8. The solidified formulations were characterized by Brunauer-Emmett-Teller (BET), powder flow properties, scanning electron microscopy, and droplet size analysis. In addition, the optimized formulations were evaluated through in vitro lipolysis and stability studies. RESULTS: The cured solid SNEDDS formula by PVP k30 showed acceptable self-emulsification and powder flow properties. XRD and DSC revealed that CN was successfully amorphized into drug-loaded S-SNEDDS. The uncured solid SNEDDS experienced negligible drug release (only 5% drug release after 2 h), while the cured S-SNEDDS showed up to 12-fold enhancement of total drug release (at 2 h) compared to the uncured counterpart. However, the cured S- SNEDDS showed considerable CN degradation and decrease in drug release upon storage in accelerated conditions. CONCLUSIONS: The implemented solidification approach offers a promising technique to minimize the adverse effect of adsorbent on drug release and accomplish improved drug release from solidified SNEDDS.
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BACKGROUND: The current study aimed to design a novel combination of lansoprazole (LNS) and curcumin (CUR) solid oral dosage form using bioactive self-nanoemulsifying drug delivery systems (Bio-SSNEDDS). METHODS: Liquid SNEDDS were prepared using the lipid-excipients: Imwitor988 (cosurfactant), Kolliphor El (surfactant), the bioactive black seed (BSO) and/or zanthoxylum rhetsa seed oils (ZRO). Liquid SNEDDS were loaded with CUR and LNS, then solidified using commercially available (uncured) and processed (cured) Neusilin® US2 (NUS2) adsorbent. A novel UHPLC method was validated to simultaneously quantify CUR and LNS in lipid-based formulations. The liquid SNEDDS were characterized in terms of self-emulsification, droplet size and zeta-potential measurements. The solidified SNEDDS were characterized by differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), scanning electron microscopy (SEM), in vitro dissolution and stability in accelerated storage conditions. RESULTS: Liquid SNEDDS containing BSO produced a transparent appearance and ultra-fine droplet size (14 nm) upon aqueous dilution. The solidified SNEDDS using cured and uncured NUS2 showed complete solidification with no particle agglomeration. DSC and XRD confirmed the conversion of crystalline CUR and LNS to the amorphous form in all solid SNEDDS samples. SEM images showed that CUR/LNS-SNEDDS were relatively spherical and regular in shape. The optimized solid SNEDDS showed higher percent of cumulative release as compared to the pure drugs. Curing NUS2 with 10% PVP led to significant enhancement of CUR and LNS dissolution efficiencies (up to 1.82- and 2.75-fold, respectively) compared to uncured NUS2-based solid SNEDDS. These findings could be attributed to the significant (50%) reduction in the micropore area% in cured NUS2 which reflects blocking very small pores allowing more space for the self-emulsification process to take place in the larger-size pores. Solid SNEDDS showed significant enhancement of liquid SNEDDS stability after 6 months storage in accelerated conditions. CONCLUSIONS: The developed Bio-SSNEDDS of CUR and LNS using processed NUS2 could be used as a potential combination therapy to improve the treatment of peptic ulcers.
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Solidified self-nanoemulsifying drug delivery systems (SNEDDS) offer strong option to enhance both drug aqueous solubility and stability. The current study was designed to evaluate the potential stabilization benefits of solidifying cinnarizine (CN) liquid SNEDDS into single and multi-layer self-nanoemulsifying pellets (SL-SNEP and ML-SNEP, respectively). The selected formulations were enrolled into accelerated, intermediate and long-term stability studies. The chemical stability was assessed based on the % of intact CN remaining in formulation. The physical stability was assessed by monitoring the in-vitro dissolution and physical appearance of the formulations. The degradation pathway of CN within lipid-based formulation was proposed to involve a hydroxylation reaction of CN molecule. The chemical stability study revealed significant CN degradation in liquid SNEDDS, SL-SNEP and ML-SNEP (lacking moisture-sealing) within all the storage conditions. In contrast, the moisture sealed ML-SNEP showed significant enhancement of CN chemical stability within the formulation. In particular, ML-SNEP coated with Kollicoat Smartseal 30D showed superior CN stabilization and no significant decrease in dissolution efficiency, at all the storage conditions. The observed stability enhancement is owing to the complete isolation between CN and SNEDDS layer as well as the effective moisture protection provided by Kollicoat Smartseal 30D. Hence, the degradation problem could be eradicated completely. The incorporation of silicon dioxide had an important role in the inhibition of pellet agglomeration upon storage. Accordingly, ML-SNEP coated with Kollicoat Smartseal 30D and/or silicon dioxide could be an excellent dosage form that combine dual enhancement of CN solubilization and stabilization.
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Cinarizina/química , Composición de Medicamentos/métodos , Sistemas de Liberación de Medicamentos/métodos , Nanopartículas/química , Formas de Dosificación , Estabilidad de Medicamentos , Emulsiones , Glicerol/análogos & derivados , Glicerol/química , Ácido Oléico/química , Povidona/química , Dióxido de Silicio/química , Solubilidad , Agua/químicaRESUMEN
Beside their solubility limitations, some poorly water-soluble drugs undergo extensive degradation in aqueous and/or lipid-based formulations. Multi-layer self-nanoemulsifying pellets (ML-SNEP) introduce an innovative delivery system based on isolating the drug from the self-nanoemulsifying layer to enhance drug aqueous solubility and minimize degradation. In the current study, various batches of cinnarizine (CN) ML-SNEP were prepared using fluid bed coating and involved a drug-free self-nanoemulsifying layer, protective layer, drug layer, moisture-sealing layer, and/or an anti-adherent layer. Each layer was optimized based on coating outcomes such as coating recovery and mono-pellets%. The optimized ML-SNEP were characterized using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), in vitro dissolution, and stability studies. The optimized ML-SNEP were free-flowing, well separated with high coating recovery. SEM showed multiple well-defined coating layers. The acidic polyvinylpyrrolidone:CN (4:1) solution presented excellent drug-layering outcomes. DSC and XRD confirmed CN transformation into amorphous state within the drug layer. The isolation between CN and self-nanoemulsifying layer did not adversely affect drug dissolution. CN was able to spontaneously migrate into the micelles arising from the drug-free self-nanoemulsifying layer. ML-SNEP showed superior dissolution compared to Stugeron® tablets at pH 1.2 and 6.8. Particularly, on shifting to pH 6.8, ML-SNEP maintained > 84% CN in solution while Stugeron® tablets showed significant CN precipitation leaving only 7% CN in solution. Furthermore, ML-SNEP (comprising Kollicoat® Smartseal 30D) showed robust stability and maintained > 97% intact CN within the accelerated storage conditions. Accordingly, ML-SNEP offer a novel delivery system that combines both enhanced solubilization and stabilization of unstable poorly soluble drugs.
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Cinarizina/química , Sistemas de Liberación de Medicamentos/métodos , Emulsionantes/química , Antagonistas de los Receptores Histamínicos H1/química , Agua/química , Disponibilidad Biológica , Rastreo Diferencial de Calorimetría , Cinarizina/metabolismo , Composición de Medicamentos/métodos , Implantes de Medicamentos , Liberación de Fármacos , Emulsionantes/metabolismo , Antagonistas de los Receptores Histamínicos H1/metabolismo , Solubilidad , Agua/metabolismo , Difracción de Rayos XRESUMEN
ABSTRACT Formulators face great challenges in adopting systematic approaches for designing self-nanoemulsifying formulations (SNEFs) for different drug categories. In this study, we aimed to build-up an advanced SNEF development framework for weakly basic lipophilic drugs, such as cinnarizine (CN). First, the influence of formulation acidification on CN solubility was investigated. Second, formulation self-emulsification in media with different pH was assessed. Experimentally designed phase diagrams were also utilized for advanced optimization of CN-SNEF. Finally, the optimized formulation was examined using cross polarizing light microscopy for the presence of liquid crystals. CN solubility was significantly enhanced upon external and internal acidification. Among the various fatty acids, oleic acid-based formulations showed superior self-emulsification in all the tested media. Surprisingly, formulation turbidity and droplet size significantly decreased upon equilibration with CN. The design was validated using oleic acid/Imwitor308/Cremophor El (25/25/50), which showed excellent self-nanoemulsification, 43-nm droplet size (for CN-equilibrated formulations), and 88 mg/g CN solubility. In contrast to CN-free formulations, CN-loaded SNEF presented lamellar liquid crystals upon 50% aqueous dilution. These findings confirmed that CN-SNEF efficiency was greatly enhanced upon drug incorporation. The adopted strategy offers fast and accurate development of SNEFs and could be extrapolated for other weakly basic lipophilic drugs.
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Solubilidad/efectos de los fármacos , Optimización de Procesos/clasificación , Cinarizina/análisis , Composición de Medicamentos/estadística & datos numéricos , Acidificación/análisisRESUMEN
Due to its extreme lipophilicity, the oral delivery of cinnarizine (CN) encounters several problems such as poor aqueous solubility and pH-dependent dissolution, which result in low and erratic bioavailability. The current study aims to design self-nanoemulsifying drug delivery systems (SNEDDS) of CN that circumvent such obstacles. Equilibrium solubility of CN was determined in a range of anhydrous and diluted lipid-based formulations. Dynamic dispersion tests were carried out to investigate the efficiency of drug release and magnitude of precipitation that could occur upon aqueous dilution. Droplet sizes of selected formulations, upon (1:1,000) aqueous dilution, were presented. The optimal formulations were enrolled in subsequent dissolution studies. The results showed that increasing lipid chain length and surfactant lipophilicity raised the formulation solvent capacity, while adding co-solvents provoked a negative influence. The inclusion of mixed glycerides and/or hydrophilic surfactants improved the drug release efficiency. Generally, no significant precipitation was observed upon aqueous dilution of the formulations. Five formulations were optimal in terms of their superior self-emulsifying efficiency, drug solubility, dispersion characteristics, and lower droplet size. Furthermore, the optimal formulations showed superior dissolution profile compared to the marketed (Stugeron®) tablet. Most importantly, they could resist the intensive precipitation observed with the marketed tablet upon shifting from acidic to alkaline media. However, SNEDDS containing medium-chain mixed glycerides showed the highest drug release rate and provide great potential to enhance the oral CN delivery. Accordingly, the lipid portion seems to be the most vital component in designing CN self-nanoemulsifying systems.
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Cinarizina/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Diseño de Fármacos , Emulsiones/administración & dosificación , Nanopartículas/administración & dosificación , Administración Oral , Cinarizina/síntesis química , Emulsiones/síntesis química , Nanopartículas/químicaRESUMEN
The study was designed to build up a database for the evaluation of the self-emulsifying lipid formulations performance. A standard assessment method was constructed to evaluate the self-emulsifying efficiency of the formulations based on five parameters including excipients miscibility, spontaneity, dispersibility, homogeneity, and physical appearance. Equilibrium phase studies were conducted to investigate the phase changes of the anhydrous formulation in response to aqueous dilution. Droplet size studies were carried out to assess the influence of lipid and surfactant portions on the resulted droplet size upon aqueous dilution. Formulations containing mixed glycerides showed enhanced self-emulsification with both lipophilic and hydrophilic surfactants. Increasing the polarity of the lipid portion in the formulation leaded to progressive water solubilization capacity. In addition, formulations containing medium chain mixed glycerides and hydrophilic surfactants showed lower droplet size compared with their long chain and lipophilic counterparts. The inclusion of mixed glycerides in the lipid formulations enormously enhances the formulation efficiency.