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ABSTRACT: Context: Ion exchange resins have ability to exchange their counter ions for ionized drug in the surrounding medium, yielding "drug resin complex." Cyclodextrin can be applied for enhancement of drug solubility and stability. Objective: Cyclodextrin inclusion complex of poorly water-soluble NSAIDs, i.e. meloxicam and piroxicam, was characterized and its novel application for improving drug loading onto an anionic exchange resin, i.e. Dowex(®) 1×2, was investigated. Methods: β-cyclodextrin (β-CD) and hydroxypropyl β-cyclodextrin (HP-β-CD) were used for the preparation of inclusion complex with drugs in solution state at various pH. The inclusion complex was characterized by phase solubility, continuous variation, spectroscopic and electrochemistry methods. Then, the drug with and without cyclodextrin were equilibrated with resin at 1:1 and 1:2 weight ratio of drug and resin. Results and discussion: Solubility of the drugs was found to increase with increasing cyclodextrin concentration and pH. The increased solubility was explained predominantly due to the formation of inclusion complex at low pH and the increased ionization of drug at high pH. According to characterization studies, the inclusion complex was successfully formed with a 1:1 stoichiometry. The presence of cyclodextrin in the loading solution resulted in the improvement of drug loading onto resin. Conclusions: Enhancing drug loading onto ion-exchange resin via the formation of cyclodextrin inclusion complex is usable in the development of ion-exchange based drug delivery systems, which will beneficially reduce the use of harmful acidic or basic and organic chemicals.
Drug Development and Industrial Pharmacy 10/2012; · 1.49 Impact Factor
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ABSTRACT: The aim of this study was to prepare, characterize and evaluate electrospun polyvinyl alcohol (PVA) and cellulose acetate (CA) nanofibers loaded with capsicum extract (CE) for use in topical skin treatments. CE, 0.5, 1 or 2 wt %, was loaded into PVA and CA electrospun fiber mats. Various properties of the CE-loaded fiber mats as well as release and skin permeation were investigated. The average diameters of these fibers ranged from 251-368 nm. The release rate of capsaicin from CE-loaded as-spun PVA was faster than that of the CA fiber mats and increased as the CE content in CE-loaded as-spun PVA and CA increased. The release kinetics of the CA and PVA fibers followed the Higuchi equation. The percentages of CE that permeated the shed snake skin with PVA and CA fiber mats containing 2 wt % CE after 24 h were 60% and 20%, respectively. The results suggest a potential use of PVA and CA nanofibers being used to control skin permeation of capsicum extract. Our research suggests the potential application of CE-loaded PVA electrospun mats as transdermal drug delivery systems.
Pharmaceutical Development and Technology 10/2012; · 1.36 Impact Factor
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ABSTRACT: The purpose of this research was to formulate nanostructured lipid carriers (NLC) for the parenteral delivery of an anticancer drug, all-trans retinoic acid (ATRA). The ATRA was incorporated into NLC by the de novo emulsification method. The effect of the formulation factor, i.e., type and oil ratio, initial ATRA concentration on physicochemical properties was determined. The anticancer efficacy of ATRA-loaded NLC on HL-60 and HepG2 cells was also studied. NLC was formulated using a blend of solid lipids (cetyl palmitate) and liquid lipids (soybean oil (S), medium-chain triglyceride (M), S/oleic acid (O; 3:1) and M/O (3:1)) at a weight ratio of 1:1. ATRA-loaded NLC had an average size of less than 200 nm (141.80 to 172.95 nm) with a narrow PDI and negative zeta potential that was within an acceptable range for intravenous injection. The results indicated that oleic acid enhanced the ATRA-loading capacity of NLC. In vitro ATRA release was only approximately 4.06% to 4.34% for 48 h, and no significant difference in ATRA release rate from all NLC formulations in accordance with the composition of the oil phase. Moreover, no burst release of the drug was observed, indicating that NLC could prolong the release of ATRA. The initial drug concentration affected the photodegradation rate but did not affect the release rate. All ATRA-loaded NLC formulations exhibited the photoprotective property. The cytotoxicity results showed that all ATRA-loaded NLC had higher cytotoxicity than the free drug and HL-60 cells were more sensitive to ATRA than HepG2 cells.
AAPS PharmSciTech 12/2011; 13(1):150-8. · 1.43 Impact Factor
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ABSTRACT: The purpose of this study was to investigate the effect of drug incorporation methods on the partitioning behavior of lipophilic drugs in parenteral lipid emulsions. Four lipophilic benzodiazepines, alprazolam, clonazepam, diazepam, and lorazepam, were used as model drugs. Two methods were used to incorporate drugs into an emulsion: dissolving the compound in the oil phase prior to emulsification (de novo emulsification), and directly adding a concentrated solution of drug in a solubilizer to the emulsion base (extemporaneous addition). Based on the molecular structures and determination of the oil and aqueous solubilities and the partition coefficients of the drugs, the lipophilicity was ranked as diazepam > clonazepam > lorazepam > alprazolam. Ultracentrifugation was used to separate the emulsion into four phases, the oil phase, the phospholipid-rich phase, the aqueous phase and the mesophase, and the drug content in each phase was determined. Partitioning of diazepam, which has the highest lipophilicity and oil solubility among the four drugs, was unaffected by the drug incorporation method, with both methods giving a high proportion of drug in the inner oil phase and the phospholipid-rich phase, compared to the aqueous phase and mesophase. Partitioning of the less lipophilic drugs (alprazolam, clonazepam, and lorazepam) in the phases of the emulsion system was dependent on the method of incorporation and the drug solubility properties. Emulsions of the three drugs prepared by de novo emulsification exhibited higher drug localization in the phospholipid-rich phase compared to those made by extemporaneous addition. With the latter method, the drugs tended to localize in the outer aqueous phase and mesophase, with less deposition in the phospholipid-rich phase and no partitioning into the inner oil phase.
AAPS PharmSciTech 01/2008; 9(2):684-92. · 1.43 Impact Factor
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ABSTRACT: Phospholipids--stabilized submicron emulsions require the addition of preservatives to destroy or inhibit the growth of microorganisms when these preparations are non-sterile products or when packed in multi-dose containers. This study examined the distribution of four paraben esters--methylparaben, ethylparaben, propylparaben, and butylparaben--that were added into submicron emulsions by de novo emulsification. The distribution of preservative compounds among different phases was determined after separation of submicron emulsions by ultracentrifugation. The compounds with higher lipophilicity were concentrated in the oil phase and phospholipids-rich phase, leading to an increase in oil droplet size. However, the effect of the paraben distribution on zeta potential and pH of emulsion fluctuated depending on the type of phospholipid used. The lower lipophilic compounds were mostly found in the aqueous phase and mesophase. These results signify the possibility that the chemical structures and lipophilicity of preservative compounds affected their distribution in phospholipid-stabilized submicron emulsions. We conclude that the higher concentration of preservatives or their combination may be required for efficient preservation of submicron emulsion products.
PDA journal of pharmaceutical science and technology / PDA 60(3):172-81.
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ABSTRACT: The objective of this study was to formulate high loading with good stability of all-trans retinoic acid (ATRA) lipid emulsion. Lipid emulsions loaded with ATRA were composed of lecithin, medium chain triglyceride and poloxamer-188 or polysorbate-80. The formulation factors in a particular type and amount of oil, emulsifier, and co-emulsifier on the physicochemical properties (i.e., particle size, size distribution, droplets surface charge, pH, percentage yield, drug release, and stability of lipid emulsions) were studied. The particle size of ATRA-loaded lipid emulsions was in the nano-size range of 124.4-378.2 nm with the narrow polydispersity index of 0.04-0.09, which decreased as the amount of co-emulsifiers was increased. The amount of ATRA released from lipid emulsions was operated using a dialysis bag. The receptor medium was ethanol:polysorbate-80:water (10:15:75), adjusted to pH 8.5. ATRA release kinetics in this study were found to follow zero-order kinetics. As the concentration of co-emulsifiers increased, the flux of ATRA released from the lipid emulsions increased. In stability studies, the higher the amount of co-emulsifiers added, the lower the crystallization of ATRA was found. The percentage yield of ATRA was retained at about 70-90% and 60-72% after storage for 60 days at 4 degrees C and 25 degrees C, respectively. These results show a successful incorporation of ATRA into lipid emulsions with high loading capacity and good stability.
PDA journal of pharmaceutical science and technology / PDA 61(6):461-71.
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ABSTRACT: The aim of this study was to investigate the enhancement of all-trans retinoic acid (ATRA) loading in nano-lipid emulsions and stability by using oleic acid. The effect of formulation factors including initial ATRA concentration and the type of oil on the physicochemical properties, that is, percentage yield, percentage drug release, and photostability of formulations, was determined. The solubility of ATRA was increased in the order of oleic acid > MCT > soybean oil > water. The physicochemical properties of ATRA-loaded lipid emulsion, including mean particle diameter and zeta potential, were modulated by changing an initial ATRA concentration as well as the type and mixing ratio of oil and oleic acid as an oil phase. The particles of lipid emulsions had average sizes of less than 250 nm and negative zeta potential. The addition of oleic acid in lipid emulsions resulted in high loading capacity. The photodegradation rate was found to be dependent on the initial drug concentration but independent of the type of oily phase used in this study. The release rates were not affected by initial ATRA concentration but were affected by the type of oil, where oleic acid showed the highest release rate of ATRA from lipid emulsions.
PDA journal of pharmaceutical science and technology / PDA. 64(2):113-23.
