Liquid Delivery System Research Articles

Evaluation of Bio-Mechanistic Behavior of Liquid Self-Microemulsifying Drug Delivery System in Biorelevant Media

The aim of the study is to mechanistically investigate the drug loci, structural integrity, chemical interactions, and absorption behavior of the liquid self-microemulsifying drug delivery system (SMEDDS). The loci of drug molecules in self-forming microemulsions in biorelevant media (fasted state simulated gastric fluid and fed state simulated intestinal fluid) were investigated by 1H and 13C nuclear magnetic resonance (NMR) spectroscopy. Chemical interactions were observed through attenuated total reflectance spectroscopy (ATR). The structural integrity of self-forming microemulsions in biorelevant media was determined by small angle X-ray scattering (SAXS) and fluorescence resonance energy transfer (FRET). Morphological features of self-forming microemulsion were determined by confocal laser scanning microscopy. In vitro, lipid digestion behavior was evaluated for particle size, zeta potential, free fatty acids (FFA), and drug released through standard protocols. In-house characterizations were determined through standard methodologies. 1H and 13C NMR revealed that drug loci were found in a majority in the oily core region in the self-forming microemulsion. The ATR signifies that no inherent chemical was observed in the liquid SMEDDS and drug-loaded self-microemulsions in the biorelevant media. Structural integrity was well maintained during the dispersive and digestive phases in the gastrointestinal lumen during lipolysis in biorelevant conditions, as revealed by SAXS and FRET. An in vitro digestion study in biorelevant conditions depicts no fluctuations in size and zeta potential with a predominant release of FFA and drug, and was to be revealed physiologically acceptable for clinical applications.

Comparison of l-Carnitine and l-Carnitine HCL salt for targeted lung treatment of pulmonary hypertension (PH) as inhalation aerosols: Design, comprehensive characterization, in vitro 2D/3D cell cultures, and in vivo MCT-Rat model of PH

Disrupted l-Carnitine (L-Car) homeostasis has been implicated in the development of pulmonary hypertension (PH). L-Car has been administered orally and intravenously causing systemic side effects. To the authors’ knowledge, there are no reports using L-Car or L-Car HCl as an inhaled aerosol through the respiratory route in a targeted manner either from dry powder inhaler (DPI) or liquid delivery system. The purpose of the comprehensive and systematic comparative study between L-Car and L-Car HCl salt was to design and develop dry powder inhalers (DPIs) of each. This was followed by comprehensive physicochemical characterization, in vitro cell viability as a function of dose on 2D human pulmonary cell lines from different lung regions and in vitro cell viability on 3D small airway epithelia human primary cells at the air-liquid interface (ALI). In addition in vitro transepithelial electrical resistance (TEER) in air-interface culture (AIC) conditions on 2D human pulmonary cell line and 3D small airway epithelia human primary cells was carried out. In vitro aerosol dispersion performance using three FDA-approved human DPI devices with different device properties was also examined. Following advanced spray drying under various conditions, two spray drying pump rates (low and medium) were found to successfully produce spray-dried L-Car powders while four spray drying pump rates (low, medium, medium-high, and high) all resulted in the production of spray-dried L-Car HCl powders. Raw L-Car and L-Car HCl were found to be crystalline. All SD powders retained crystallinity following spray drying and polymorphic interconversion in the solid-state was identified as the mechanism for retaining crystallinity after the advanced spray drying process. All SD powders aerosolized readily with all three human DPI devices. However, the in vitro dispersion parameters for the SD powders was not conducive for in vivo administration to rats in DPIs due to hygroscopicity and nanoaggreation. In vivo rat studies were successfully accomplished using inhaled liquid aerosols. Safety was successfully demonstrated in vivo in healthy Sprague Dawley rats. Furthermore, therapeutic efficacy was successfully demonstrated in vivo in the monocrotaline (MCT)-rat model of PH after two weeks of daily L-Car inhalation aerosol treatment.

Enhanced Oral Bioavailability and Improved Biological Activities of a Quercetin/Resveratrol Combination Using a Liquid Self-Microemulsifying Drug Delivery System.

Both quercetin and resveratrol are promising plant-derived compounds with various well-described biological activities; however, they are categorized as having low aqueous solubility and labile natural compounds. The purpose of the present study was to propose a drug delivery system to enhance the oral bioavailability of combined quercetin and resveratrol. The suitable self-microemulsifying formulation containing quercetin together with resveratrol comprised 100 mg Capryol 90, 700 mg Cremophor EL, 200 mg Labrasol, 20 mg quercetin, and 20 mg resveratrol, which gave a particle size of 16.91 ± 0.08 nm and was stable under both intermediate and accelerated storage conditions for 12 months. The percentages of release for quercetin and resveratrol in the self-microemulsifying formulation were 75.88 ± 1.44 and 86.32 ± 2.32%, respectively, at 30 min. In rats, an in vivo pharmacokinetics study revealed that the area under the curve of the self-microemulsifying formulation containing quercetin and resveratrol increased approximately ninefold for quercetin and threefold for resveratrol compared with the unformulated compounds. Moreover, the self-microemulsifying formulation containing quercetin and resveratrol slightly enhanced the in vitro antioxidant and cytotoxic effects on AGS, Caco-2, and HT-29 cells. These findings demonstrate that the self-microemulsifying formulation containing quercetin and resveratrol could successfully enhance the oral bioavailability of the combination of quercetin and resveratrol without interfering with their biological activities. These results provide valuable information for more in-depth research into the utilization of combined quercetin and resveratrol.

Liquid and Solid Self-Emulsifying Drug Delivery Systems (SEDDs) as Carriers for the Oral Delivery of Azithromycin: Optimization, In Vitro Characterization and Stability Assessment.

Azithromycin (AZM) is a macrolide antibiotic used for the treatment of various bacterial infections. The drug is known to have low oral bioavailability (37%) which may be attributed to its relatively high molecular weight, low solubility, dissolution rate, and incomplete intestinal absorption. To overcome these drawbacks, liquid (L) and solid (S) self-emulsifying drug delivery systems (SEDDs) of AZM were developed and optimized. Eight different pseudo-ternary diagrams were constructed based on the drug solubility and the emulsification studies in various SEDDs excipients at different surfactant to co-surfactant (Smix) ratios. Droplet size (DS) < 150 nm, dispersity (Đ) ≤ 0.7, and transmittance (T)% > 85 in three diluents of distilled water (DW), 0.1 mM HCl, and simulated intestinal fluids (SIF) were considered as the selection criteria. The final formulations of L-SEDDs (L-F1(H)), and S-SEDDs (S-F1(H)) were able to meet the selection requirements. Both formulations were proven to be cytocompatible and able to open up the cellular epithelial tight junctions (TJ). The drug dissolution studies showed that after 5 min > 90% and 52.22% of the AZM was released from liquid and solid SEDDs formulations in DW, respectively, compared to 11.27% of the pure AZM, suggesting the developed SEDDs may enhance the oral delivery of the drug. The formulations were stable at refrigerator storage conditions.

An integrated QbD based approach of SMEDDS and liquisolid compacts to simultaneously improve the solubility and processability of hydrochlorthiazide

Hydrochlorothiazide (HCTZ) is a class IV BCS drug that exhibits varying bioavailability due to poor solubility and low permeability. The first part of the present investigation was aimed to prepare liquid self-microemulsifying drug delivery system (SMEDDS) of HCTZ to improve its dissolution properties. The liquid SMEDDS was subsequently converted to self-microemulsifying tablets (SMETs) by using the liquisolid technique to facilitate the manufacturing process. Based on the solubility study and ability to form transparent microemulsion upon dilution, oleic acid, tween-20, and propylene glycol were selected as oil, surfactant, and co-surfactant respectively to form liquid SMEDDS. The central composite design was used to investigate the effect of changes in formulation composition on critical product characteristics and to optimize the SMEDDS formualtion. Neusilin US2 and Aerosil-200 were selected as carrier and coating material to prepare SMETs as they displayed the highest flowable liquid potential among all tested excipients. The prepared SMETs have acceptable tableting properties (flowability, compressibility, and compactibility) and were able to preserve self microemulsifying properties of entrapped SMEDDS formulation. The results of DSC and XRD studies suggested that better dissolution properties of SMETs formulation compared to pure drug and marketed products was possibly due to the drug either being molecularly dispersed form or presence in the amorphous state within the formulation.

DEVELOPMENT AND EVALUATION OF ZIPRASIDONE LOADED SOLID SELF-MICRO EMULSIFYING DRUG DELIVERY SYSTEM

Solid self-micro emulsification technique is the new approach for poorly water-soluble and poorly bioavailable drugs by allowing the drug substance to be incorporated into the oil phase and thus having the ability to permeate the GI membrane to a faster extent. Oleic acid, Tween 80, methanol and colloidal silicon dioxide were used as penetrant, surfactant, co-surfactant and adsorbent, respectively. The interaction between drug and excipients was examined by differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR). The results of DSC and FTIR studies did not reveal any possible drug-excipient interactions. The conversion of liquid self-microemulsifying drug delivery system (SMEDDS) into the solid SMEDDS increases the stability of the emulsion formulation achieved by physical adsorption of an adsorbent material. The release of drug from SMEDDS formulation is justified by in-vitro dissolution studies. SMEDDS increases the solubility of the drug and improves the bioavailability, without disturbing gastrointestinal transit. SMEDDS has the potential to provide a useful oral solid dosage form for the poorly water-soluble drug ziprasidone.

Development of Solid Self – Nanoemulsified Drug Delivery System Containing Rosuvastatin

This study aims to solidify the self-nanoemulsifying drug delivery system with rosuvastatin (SNEDDS Ros) for application in solid dosage forms. The liquid SNEDDS Ros system is solidified by granulation and spray drying methods. Solid SNEDDS Ros was evaluated on the drug content, the Carr index, nanoemulsification efficiency and several criteria of nanoemulsion, formed after emulsification of solid SNEDDS Ros, such as droplet size, polydispersion index (PDI), the drug proportion in the oil phase. The study results show that solid SNEDDS Ros, prepared by granulation method using Prosolv SMCC 90 as an adsorbent, had good flowability with the Carr index of about 15. The nanoemulsion, obtained after emulsification of the solid SNEDDS, had an average particle size of 15 nm, PDI less than 0.2, drug nanoemulsified efficiency of 94 % and drug proportion in the oil phase of 84%.&#x0D; Keywords&#x0D; Rosuvastatin, SNEDDS, Solid SNEDDS, solidification.&#x0D; References&#x0D; [1] A.G. Olsson, F. McTaggart, and A. Raza, Rosuvastatin: A Highly Effective New HMG-CoA Reductase Inhibitor. Cardiovasc. Drug Rev., 20 (2006) 303–328. https://doi.org/10.1111/j.1527-3466.2002.tb00099.x[2] A.M. Kassem, H.M. Ibrahim, and A.M. Samy, Development and optimisation of atorvastatin calcium loaded self-nanoemulsifying drug delivery system (SNEDDS) for enhancing oral bioavailability: in vitro and in vivo evaluation. J. Microencapsul 34 (2017) 319–333. https://doi.org/10.1080/02652048.2017.1328464[3] M.N. Ahsan and P.R. Prasad Verma, Solidified self nano-emulsifying drug delivery system of rosuvastatin calcium to treat diet-induced hyperlipidemia in rat: in vitro and in vivo evaluations. Ther. Deliv 8 (2017) 125–136. https://doi.org/10.4155/tde-2016-0071[4] S. Verma, S.K. Singh, P. R. P. Verma, and M. N. Ahsan, Formulation by design of felodipine loaded liquid and solid self nanoemulsifying drug delivery systems using Box-Behnken design. Drug Dev. Ind. Pharm. 40 (2014) 1358–1370. https://doi.org/10.3109/03639045.2013.819884[5] M.S. Reddy, Formulation and In Vitro Characterization of Solid-self Nanoemulsifying Drug Delivery System of Atorvastatin Calcium. Asian J. Pharm. 11 (2018) 991-999. https://dx.doi.org/10.22377/ajp.v11i04.1771.[6] N. Kulkarni, N. Ranpise, and G. Mohan, Development and evaluation of solid self nano-emulsifying formulation of rosuvastatin calcium for improved bioavailability. Trop. J. Pharm. Res. 14 (2015) 575–582. https://doi.org/10.4314/tjpr.v14i4.3[7] A.O. Kamel and A.A. Mahmoud, Enhancement of human oral bioavailability and in vitro antitumor activity of rosuvastatin via spray dried self-nanoemulsifying drug delivery system. J. Biomed. Nanotechnol. 9 (2013) 26–39. https://doi.org 10.1166/jbn.2013.1469.[8] H.A. Abo Enin and H.M. Abdel-Bar, Solid super saturated self-nanoemulsifying drug delivery system (sat-SNEDDS) as a promising alternative to conventional SNEDDS for improvement rosuvastatin calcium oral bioavailability. Expert Opin. Drug Deliv. 13 (2016) 1513–1521. https://doi.org/10.1080/17425247.2016.1224845&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D;

Exploring role of probiotics and Ganoderma lucidum extract powder as solid carriers to solidify liquid self-nanoemulsifying delivery systems loaded with curcumin

Solid self-nanoemulsifying drug delivery system (S-SENDDS) containing Curcumin (CRM) were prepared using combination of Ganoderma lucidum extract powder (GLEP) and probiotics (PB) as carriers. Liquid SNEDDS containing CRM were prepared by mixing Capmul MCM, Labrafil M1944CS, Tween 80 and Transcutol P. These were further spray dried and finally converted into spheroids. The droplet size of reconstituted S-SNEDDS powder and spheroids was found in the range of 35 to 37 nm, zeta potential in the range of - 21.48 to -23.22 mV and drug loading in the range of 95-96%. The release of drug from formulations was found to be more than 90%. Similarly, significant improvement (p < 0.05) in permeability of CRM was observed through SNEDDS using Caco2 cell lines. The non-significant difference (p> 0.05) in drug loading, droplet size, dissolution rate and angle of repose between L-SNEDDS and S-SNEDDS indicated the potential of GLEP-PB to produce stable SNEDDS.

Formulation and Characterization of Piroxicam as Self-Nano Emulsifying Drug Delivery System

Piroxicam (PIR) is a nonsteroidal anti-inflammatory drug of oxicam category, used in gout, arthritis, as well as other inflammatory conditions (topically and orally). PIR is practically insoluble in water, therefore the aim is prepare and evaluate piroxicam as liquid self-nanoemulsifying drug delivery system to enhance its dispersibility and stability. The Dispersibilty and Stability study have been conducted in Oil, Surfactant and Co-surfactant for choosing the best materials to dissolve piroxicam. The pseudo ternary phase diagrams have been set at 1:1, 2:1, 3:1 as well as 4:1 ratio of surfactants and co-surfactants, also there are 4 formulations were prepared by using various concentrations of transcutol HP, cremophore EL and triacetin oil. All the constructed prepared formulas have been assessed for in vitro drug dissolution, thermodynamic stability, polydispersity index, robustness to dilution, particle size distribution, drug content, and the dispersibility and emulsification time.From the presented research concluded that the self-nanoemulsifying drug delivery system is the convenient method for improving Dispersibilty and Stability of piroxicam.&#x0D; Keywords: Pseudo-ternary phase diagram, Dissolution rate, SNEDDS, Piroxicam.

Fast understanding of phases and phase separation in liquid crystal drug delivery systems using deuterium solid-state NMR

Characterization of lipid based (SPC/GDO/H2O) liquid crystal (LC) drug delivery system is non-trivial and highly complex, especially when multiple and intermediate phases are present. The phase behavior of such mixtures during hydration or delivery is still poorly understood and therefore, characterizing these systems is crucially important towards controlling their function and enhancing the understanding of their drug release behavior. Current work has established an easy way to identify liquid crystal phases and phase mixtures using deuterium (2H) solid-state nuclear magnetic (NMR) spectroscopy under static conditions without disrupting the three dimensional structure and phases, as magic-angle spinning (MAS) could lead to disruption of the phases. Small angle X-ray scattering (SAXS) technique and optical microscopy were also employed to corroborate the study.

Development and Validation of UV Spectroscopic Method for Estimation of Fisetin in Self Nanoemulsifying Drug Delivery System

Fisetin is a polyphenolic flavonoid which has been reported various pharmacological activities as a crude extract and in formulation form. This study was designed to develop and validate a simple and cost effective method for the estimation of fisetin in the liquid self nanoemulsifying drug delivery system (L-SNEDDS). Solutions having different concentration of fisetin were prepared in methanol to develop the calibration curve. The solutions were scanned at 362nm by using UV-spectrophotometer. Similarly, for validation of method recovery of drug was measured at three levels 80%, 100% and 120% of the mid concentration and data was recorded. Further, this method was used to measure the drug loading in L-SNEDDS of fisetin. The data was found to be linear in the range of 4–12μg/mL with regression coefficient of 0.999. The recovery of drug in the range of 95% to 105% indicated the accuracy of the method. The percentage relative standard deviation among all the responses was found to be less than 2% indicating the precision of the method. The LOD and LOQ was found to be 0.28 and 0.86μg/mL respectively. Drug loading in the L-SNEDDS was found to be 93.66%. A simple, accurate and cost-effective method for the estimation of the fisetin in pharmaceutical dosage forms was developed and validated using ultra violet spectroscopy.

Design and in vivo Evaluation of Manidipine by Self-Nanoemulsifying Drug Delivery Systems

The current research is aimed at developing liquid self-nanoemulsifying drug delivery system (liquid-SNEDDS) of Manidipine for enhanced solubility and oral bioavailability. The Manidipine SNEDDS are formulated with excipients comprising of Capmul MCM (oil phase), Transcutol P (surfactant) Lutrol L 300 as co-surfactant. The prepared fifteen formulations of Manidipine SNEDDS analysed for emulsification time, percentage transmittance, particle size, in vitro drug release, and stability studies. In vivo pharmacokinetic studies of the optimized formulation were carried out in Wistar rats in comparison with control (pure drug). The morphology of Manidipine SNEDDS indicates spherical shape with uniform particle distribution. The percentage drug release from optimized formulation F14 is 98.24 ± 5.14%. The particle size F14 formulation was 22.4 nm and Z-Average 23.3 nm. The PDI and zeta potential of Manidipine SNEDDS optimized formulation (F14) were 0.313 and-5.1mV respectively. From in vivo bioavailability data the optimized formulation exhibited a significantly greater Cmax and Tmax of the SNEDDS was found to be 3.42 ± 0.46ng/ml and 2.00 ± 0.05 h respectively. AUC0-∞ infinity for formulation was significantly higher (11.25 ± 3.45 ng.h/ml) than pure drug (7.45 ± 2.24ng. h/ml). Hence a potential SNEDDS formulation of Manidipine developed with enhanced solubility and bioavailability.

A Cryoinjury Model to Study Myocardial Infarction in the Mouse.

The use of animal models is essential for developing new therapeutic strategies for acute coronary syndrome and its complications. In this article, we demonstrate a murine cryoinjury infarct model that generates precise infarct sizes with high reproducibility and replicability. In brief, after intubation and sternotomy of the animal, the heart is lifted from the thorax. The probe of a handheld liquid nitrogen delivery system is applied onto the myocardial wall to induce cryoinjury. Impaired ventricular function and electrical conduction can be monitored with echocardiography or optical mapping. Transmural myocardial remodeling of the infarcted area is characterized by collagen deposition and loss of cardiomyocytes. Compared to other models (e.g., LAD-ligation), this model utilizes a handheld liquid nitrogen delivery system to generate more uniform infarct sizes.

Dietary Curcumin: Correlation between Bioavailability and Health Potential.

The yellow pigment curcumin, extracted from turmeric, is a renowned polyphenol with a broad spectrum of health properties such as antioxidant, anti-inflammatory, anti-cancer, antidiabetic, hepatoprotective, anti-allergic, anti-dermatophyte, and neuroprotective. However, these properties are followed by a poor pharmacokinetic profile which compromises its therapeutic potential. The association of low absorption by the small intestine and the extensive reductive and conjugative metabolism in the liver dramatically weakens the oral bioavailability. Several strategies such as inhibition of curcumin metabolism with adjuvants as well as novel solid and liquid oral delivery systems have been tried to counteract curcumin poor absorption and rapid elimination from the body. Some of these drug deliveries can successfully enhance the solubility, extending the residence in plasma, improving the pharmacokinetic profile and the cellular uptake.

Proactive Contamination Control for Sub 10nm Particle in Advanced Semiconductor Manufacturing

Advanced Semiconductor Manufacturing has reached the limits of metrology measuring contamination and defects on both the wafers and in the high purity materials (i.e., killer size particles in liquid chemicals and ultrapure water). Furthermore, ability of the most advanced filters to control particles in sub-10nm range is also limited. High purity materials used in liquid delivery systems have never been qualified for sub-10nm size particles. Finally, particle shedding of sub-10nm particles from high-purity components located post-filter cannot be directly measured and only be estimated using power-law extrapolation. Yield Enhancement IFT (international focus team) of IRDS (International Roadmap for Devices and Systems) is working together with the Liquid Chemical Committee of SEMI Standards to establish the methodology to enable proactive technology management in the space of contamination control. This presentation will provide the most recent experimental data generated by UPW IRDS team and SEMI Standards Liquid Chemical task forces, demonstrating the issues related to the contamination occurrence. The presentation will also include information about the SEMI standards and corresponding systematic approach that supports supply chain effort for developing and commercialization of new solutions to proactively address the contamination issues.

Formulation and characterization of novel lipid-based drug delivery systems containing polymethacrylate polymers as solid carriers for sustained release of simvastatin

Formulation of lipid-based drug delivery systems is recognized as a promising strategy to increase bioavailability of simvastatin (SV). The purpose of this study was to formulate advantageous lipid-based drug delivery systems for pH-controlled release of SV using polymethacrylate polymers (Eudragit®) as carriers. Liquid SV-loaded self-microemulsifying drug delivery systems (SMEDDS), composed of oils (PEG 300 oleic glycerides, propylene glycol monocaprylate, or propylene glycol monolaurate), surfactant (PEG 400 caprylic/capric glycerides) and cosurfactant (PEG-15 hydroxystearate), were characterized in terms of emulsification time, robustness to dilution, and droplet size. To enable targeted SV release at desired pH, the liquid SMEDDS were mixed with solid carriers, Eudragit® L100 and/or Eudragit® S100. The resulting gel-like lipid-based drug delivery systems were transparent and ductile, and exhibited viscoelastic rheological properties. In vitro dissolution data indicated sustained SV release in pH medium corresponding to distal ileum. The simulation results revealed that sustained SV release from the designed systems is expected to increase SV bioavailability. Overall, our results demonstrate that sustained-release drug delivery systems, composed of liquid SMEDDS and polymethacrylate carriers (Eudragit® polymers), have the potential to enhance oral bioavailability of drugs with preferred absorption site in the pH medium corresponding to distal ileum.

DESIGN AND EVALUATION OF SELF-NANOEMULSIFYING DRUG DELIVERY SYSTEMS OF MANIDIPINE FOR ENHANCEMENT OF SOLUBILITY

Objective: The present work is aimed at developing liquid self-nanoemulsifying drug delivery system (liquid-SNEDDS) of manidipine.&#x0D; Methods: The manidipine SNEDDS is formulated with excipients comprising Capmul MCM as oil phase, Transcutol P as surfactant, and Lutrol L 300 as cosurfactant. The prepared fifteen formulations of manidipine SNEDDS were performed for emulsification time, percentage transmittance, particle size, drug release, in vitro dissolution and stability studies. Ternary phase diagram plotted using Chemix software.&#x0D; Results: The optimized manidipine liquid SNEDDS formulation (F14) subjected to drug-excipient compatibility studies by Fourier-transform infrared spectroscopy and characterized for particle size, zeta potential, scanning electron microscopy, and stability studies. The morphology of manidipine SNEDDS indicates spherical shape with uniform particle distribution. The percentage drug release from optimized formulation F14 (98.24±5.14%) was higher than that of pure drug (39.17±2.98%). The stability data indicated no noticeable change in drug content, emulsifying properties, drug release, and appearance.&#x0D; Conclusion: Hence, a potential SNEDDS formulation of manidipine developed with enhanced solubility, dissolution rate, and bioavailability.

Proactive Contamination Control for Sub 10nm Particle in Advanced Semiconductor Manufacturing

Advanced Semiconductor Manufacturing has reached the limits of metrology measuring some critical contamination parameters and defects on both the wafers and in the high purity materials. Ability of the advanced filters to control particles sub-10nm is limited, while high purity materials used in liquid delivery systems have never been qualified for such small particles. To cope with the metrology gaps, the Yield Enhancement (YE) focus team of IRDS (International Roadmap for Devices and Systems) has defined a new process of proactive technology management in the space of contamination control. This publication provides an overview of the process including the most recent experimental data generated by YE IRDS team and SEMI Liquid Chemical task forces in support to the proactive contamination control. It also offers examples of how SEMI standards help supply chain in developing new solutions to proactively address critical contamination issues.

Novel oral dosage regimen based on self-nanoemulsifying drug delivery systems for codelivery of phytochemicals – Curcumin and thymoquinone

BackgroundCurcumin and Thymoquinone are very well-known phytochemicals for their potent anti-inflammatory and anticancer properties. The major challenges for curcumin is its poor aqueous solubility and erratic oral bioavailability. ObjectiveTo develop a novel liquid self-nanoemulsifying drug delivery system (SNEDDS) containing curcumin and thymoquinone and further converted into a solid dosage form using adsorbents Syloid® and Neusilin® as the solid carrier. MethodsThe characterization of the liquid and solid SNEDDS was performed by particle size & zeta potential analysis, scanning electron microscopy, differential scanning calorimetry, fourier transform infrared spectroscopy and X-ray powder diffraction. The drug loading, and in vitro release studies were carried out to investigate the efficiency of curcumin release from SNEDDS. ResultsThe liquid SNEDDS containing black seed oil showed excellent self-emulsification performance with transparent appearance. The results of characterization studies showed that solidification using 50% (w/w) Syloid® and Neusilin® in the liquid formulation yield free flowing powder with no agglomeration but Neusilin® produced smooth granules than Syloid® and kept the drugs stable in amorphous state. In vitro dissolution studies indicated that liquid SNEDDS formulations of F4 and its solid SNEDDS using Neusilin® provided high dissolution efficiency and reproducibility for curcumin and thymoquinone. However, Neusilin® showed higher rate of dissolution (more than 65%, p < 0.05) compared to Syloid® for curcumin. ConclusionsCurcumin loaded-SNEDDS formulation containing thymoquinone in liquid & solid dosage forms were successfully developed with an increased drug loading and dissolution rate, which could be the potential combined delivery system for various anti-inflammatory and anti-cancer treatments.

Improved oral bioavailability of myricitrin by liquid self-microemulsifying drug delivery systems

This study aimed to prepare a self-microemulsifying drug delivery system loaded with myricitrin (M-SMEDDS) to improve the low oral bioavailability of myricitrin. Prepared M-SMEDDS consisted of an oil phase (ethyl oleate), a surfactant (Cremophor EL35) and a co-surfactant (dimethyl carbinol). M-SMEDDS was characterized using the particle size, zeta potential and encapsulation efficiency, while the pharmacokinetics studies were also investigated. The prepared M-SMEDDS exhibited stable physicochemical properties with a small average droplet size (21.68 ± 0.15 nm), negative zeta potential (−23.17 ± 1.03 mV) and high encapsulation efficiency (92.73%). The in vitro release study showed that myricitrin was significantly released from M-SMEDDS compared with the free myricitrin. The relative oral bioavailability of M-SMEDDS was 2.47-fold higher than that of the free drug. These results indicated that the preparation, in vitro and in vivo studies of M-SMEDDS could obviously improve the solubility and oral bioavailability of myricitrin. This study therefore provides preliminary evidence for further clinical research and application of M-SMEDDS.