Increased dissolution rate and oral bioavailability of hydrophobic drug glyburide tablets produced using supercritical CO2 silica dispersion technology

Guan, Jibin; Han, Jie; Zhang, Dong; Chu, Chunxia; Liu, Hongzhuo; Sun, Jin; Zhang, Tianhong

doi:10.1016/j.ejpb.2013.10.008

Cited by 29 publications

(12 citation statements)

References 25 publications

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“…8,19 Glyburide (GBD), chemical name N-[4-(β-(2-methoxy-5-chlorobenzamido)-ethyl)-benzenesulfonyl]-N-cyclohexylurea, 20 is a class II Biopharmaceutical Classification System second-generation sulfonylurea drug that is orally administered to control blood glucose levels in type II diabetic patients. 21,22 Due to its poor aqueous solubility and dissolution rate, GBD shows low and erratic oral bioavailability. 23 Different strategies were investigated and published to enhance the dissolution rate and bioavailability of GBD.…”

Section: Introductionmentioning

confidence: 99%

<p>Engineering of solidified glyburide nanocrystals for tablet formulation via loading of carriers: downstream processing, characterization, and bioavailability</p>

Ali

Hanafy

Alqurshi

2019

IJN

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Introduction: Presenting poorly water-soluble drugs as nanoparticles has shown to be an effective technique in enhancing drug dissolution rate, intrinsic solubility, and thus oral bioavailability. Nevertheless, working with nanoparticles introduces many challenges, one of which is their physical instability. Formulating nanoparticles into a solid dosage form may overcome such challenges and thus unlock the potential benefits of nanosizing. Methods: The current work investigates the possibility of developing a novel solid dosage form, with enhanced dissolution rate, whereby nanocrystals (~400 nm) of the class II Biopharmaceutical Classification System drug, glyburide (GBD) were fabricated through combined precipitation and homogenization procedures. Using a novel, but scalable, spraying technique, GBD nanocrystals were loaded onto commonly used tablet fillers, water-soluble lactose monohydrate (LAC), and water insoluble microcrystalline cellulose (MCC). Conventional tableting processes were then used to convert the powders generated into a tablet dosage form. Results: Studies of redispersibility showed considerable preservation of size characteristics of GBD nanocrystals during downstream processing with redispersibility indices of 105 and 118 for GBD-LAC and GBD-MCC, respectively. Characterization by differential scanning calorimetry, powder X-ray diffraction, and scanning electron microscopy showed that the powders generated powders contained nanosized crystals of GBD which adhered to carrier surfaces. Powder flowability was characterized using Hausner ratio (HR) and Carr's index (CI). GBD-LAC-loaded particles exhibited poor flowability with CI and HR of 37.5% and 1.60, respectively, whilst GBD-MCC particles showed a slightly improved flowability with CI and HR of 26.47% and 1.36, respectively. The novel tablet dosage form met US Pharmacopeia specifications, including drug content, hardness, and friability. Conclusion: Higher dissolution rates were observed from the nanocrystal-based tablets compared to the microsized and commercial drug formulations. Moreover, the novel nanocrystal tablet dosage forms showed enhanced in vivo performance with area under the plasma concentrationtime curve in the first 24 hours values 1.97 and 2.24 times greater than that of marketed tablets.

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Section: Introductionmentioning

confidence: 99%

<p>Engineering of solidified glyburide nanocrystals for tablet formulation via loading of carriers: downstream processing, characterization, and bioavailability</p>

Ali

Hanafy

Alqurshi

2019

IJN

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“…FTIR spectra of a drug, a physical mixture of drug and excipients, were recorded using KBr discs on a Perkin-Elmer FTIR spectrometer. Spectrum range was 4,000-400/cm [14][15][16][17].…”

Section: Fourier-transform Infrared Spectroscopy (Ftir)mentioning

confidence: 99%

“…Thermal properties of a drug, a physical mixture of drug and excipients, were investigated by DSC on a thermal analyzer (DSC-Thermal Analysis: Shimadzu Corporation). About 20 mg of each sample was heated from room temperature to 300°C at a rate of 10°C/min under nitrogen [14][15][16][17].…”

Section: Differential Scanning Calorimeter (Dsc)mentioning

confidence: 99%

Investigation of Critical Material Attributes of Nanocellulose in Tablets

Vora

Shah

2019

Asian J Pharm Clin Res

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Objective: The present work aims to compare powder flow properties and post-compression characteristics of acid hydrolysis nanocellulose (AH-NC) a novel excipient with microcrystalline cellulose (MCC PH200) to demonstrate the application and performance of AH-NC. Methods: I-optimal design was applied separately for both the excipient, i.e., MCC PH200 and AH-NC. Independent variables were MCC PH200 as diluent (X1), AH-NC as diluent (X1), starch as disintegrant (X2), and PVP K30 as dry binder (X3). The dependent variables in design were Carr’s index (CI) (R1), angle of repose (AR) (R2), hardness (R3), friability (R4), disintegration time (DT) (R5), and T90 (R6). Results: Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry studies showed the compatibility of the drug with an excipient. CI was found in the range of 8%–17.84% for MCC PH200 and 5.25%–11.94% for AH-NC. AR was found in the range of 31.48–37.66 for MCC PH200 and 29.62–35.30 for AH-NC. The values of friability, DT, and T90 were almost identical in both the cases. Conclusion: Not only does AH-NC demonstrates better flow properties but also problems of weight variation and content uniformity are not observed when compared to MCC PH200. Hence, AH-NC is more suitable as an excipient for modern high-speed rotary tablet press.

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“…Pancreatic 100 beta cells also express Sur1 receptors (Panten et al, 1996) meaning that the drug effects on 101 spinal cord endothelial (and other) cells are mediated via the same mechanism as that on blood 102 glucose. Therefore, the main safety concern with use of this drug for spinal cord injury is 103 hypoglycemia.104 105 The safety of oral glyburide in healthy dogs has been evaluated previously (Guan et al, 2014; 106 Liu et al, 2014; http://products.sanofi.ca/en/diabeta.pdf). In this study we wished to extend these 107 assessments into a cohort of dogs that had spinal cord injuries for which they were undergoing 108 investigation and surgery because these other interventions and the lesion itself may alter blood 109 drug concentrations or risk of adverse effects.…”

mentioning

confidence: 99%

“…104 105 The safety of oral glyburide in healthy dogs has been evaluated previously (Guan et al, 2014; 106 Liu et al, 2014; http://products.sanofi.ca/en/diabeta.pdf). In this study we wished to extend these 107 assessments into a cohort of dogs that had spinal cord injuries for which they were undergoing 108 investigation and surgery because these other interventions and the lesion itself may alter blood 109 drug concentrations or risk of adverse effects.…”

mentioning

confidence: 99%

Peer Review #2 of "Pharmacokinetics and safety of oral glyburide in dogs with acute spinal cord injury (v0.1)"

Simard¹

2018

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Background. Glyburide (also known as glibenclamide) is effective in reducing the severity of tissue destruction and improving functional outcome after experimental spinal cord injury in rodents and so has promise as a therapy in humans. There are many important differences between spinal cord injury in experimental animals and in human clinical cases, making it difficult to introduce new therapies into clinical practice. Spinal cord injury is also common in pet dogs and requires new effective therapies, meaning that they can act as a translational model for the human condition while also deriving direct benefits from such research. In this study we investigated the pharmacokinetics and safety of glyburide in dogs with clinical spinal cord injury. Methods. We recruited dogs that had incurred an acute thoracolumbar spinal cord injury within the previous 72 hours. These had become acutely non-ambulatory on the pelvic limbs and were admitted to our veterinary hospitals to undergo anesthesia, cross sectional diagnostic imaging, and surgical decompression. Oral glyburide was given to each dog at a dose of 75 mcg/kg. In 5 dogs, we measured blood glucose concentrations for 10 hours after a single oral dose. In 6 dogs, we measured serum glyburide and glucose concentrations for 24 hours and estimated pharmacokinetic parameters to estimate a suitable dose for use in a subsequent clinical trial in similarly affected dogs. Results. No detrimental effects of glyburide administration were detected in any participating dog. Peak serum concentrations of glyburide were attained at a mean of 13 hours after dosing, and mean apparent elimination half-life was approximately 7 hours. Observed mean maximum plasma concentration was 31 ng/mL. At the glyburide dose administered there was no observable association between glyburide and glucose concentrations in blood. Discussion. Our data suggest that glyburide can be safely administered to dogs that are undergoing anesthesia, imaging and surgery for treatment of their acute spinal cord injury and can attain clinically-relevant serum concentrations without developing hazardous hypoglycemia.PeerJ reviewing PDF | Manuscript to be reviewed Serum glyburide concentrations achieved in this study suggest that a loading dose of 150 mcg/kg followed by repeat doses of 75 mcg/kg at 8-hourly intervals would lead to serum glyburide concentrations of 25-50 ng/mL within an acceptably short enough period after oral administration to be appropriate for a clinical trial in canine spinal cord injury.Manuscript to be reviewed 21 Abstract 22 23 Background. Glyburide (also known as glibenclamide) is effective in reducing the severity of 24 tissue destruction and improving functional outcome after experimental spinal cord injury in 25 rodents and so has promise as a therapy in humans. There are many important differences 26 between spinal cord injury in experimental animals and in human clinical cases, making it 27 difficult to introduce new therapies into clinical practice. Spinal cord injury is also common in 2...

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Increased dissolution rate and oral bioavailability of hydrophobic drug glyburide tablets produced using supercritical CO2 silica dispersion technology

Cited by 29 publications

References 25 publications

<p>Engineering of solidified glyburide nanocrystals for tablet formulation via loading of carriers: downstream processing, characterization, and bioavailability</p>

<p>Engineering of solidified glyburide nanocrystals for tablet formulation via loading of carriers: downstream processing, characterization, and bioavailability</p>

Investigation of Critical Material Attributes of Nanocellulose in Tablets

Peer Review #2 of "Pharmacokinetics and safety of oral glyburide in dogs with acute spinal cord injury (v0.1)"

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