Development of novel prasugrel base microsphere-loaded tablet with enhanced stability: Physicochemical characterization and in vivo evaluation in beagle dogs

Lee

Bulletin Korean Chem Soc

et al. 2019

Self Cite

The purpose of this study was to improve the chemical stability of D-cycloserine via tablet form containing an alkali stabilizer. The influence of alkalizing agents on the stability of D-cycloserine was investigated at 60 C/75% RH for 2 days. The drug stability was evaluated with the D-cycloserine-loaded tablets prepared with various amounts of magnesium oxide using direct compression method. Compared to Dcycloserine powder and a commercial D-cycloserine-loaded product, the long-term drug stability on the chosen tablet was assessed at 40, 60, and 40 C/75% RH during 6 months. Amongst the stabilizers investigated, magnesium oxide most improved the stability of D-cycloserine at the accelerated stress condition. The magnesium oxide/drug ratio of 1 and 2 showed higher remaining drug concentrations than those less than 0.5; however, two formers gave no significant difference in the remaining drug concentrations. Amongst the tablets tested, the formulation composed of D-cycloserine, magnesium oxide, and talc at the weight ratio of 250/250/5 most increased the stability of D-cycloserine. Additionally, due to the alkali and water-proofing property of magnesium oxide, this tablet improved the stability of D-cycloserine compared to the drug powder and commercial product. Hence, this novel tablet with enhanced drug stability would be a candidate for oral pharmaceutical product of D-cycloserine.

Section: Resultsmentioning

confidence: 86%

Enhanced Chemical Stability of D‐Cycloserine via Tablet Form Containing Magnesium Oxide as an Alkali Stabilizer

Lee

Bulletin Korean Chem Soc

et al. 2019

Self Cite

“…In particular, the former greatly improved (3.4-and 3.2-fold, respectively), the AUC compared to the latter products. Our results suggest that the enhanced oral bioavailability of the S-SNEDDS is provided by improved drug solubility and dissolution (Kim et al, 2015(Kim et al, , 2016d.…”

Section: Pharmacokineticsmentioning

confidence: 73%

“…Calcium silicate ( Figure 3(B-a) ) and SLS ( Figure 3(B-b) ) had a pattern consistent with an intrinsically crystalline nature (Kim et al., 2016b ). HPMC ( Figure 3(B-c) ) showed relatively weak peaks, which were negligible and not distinctive (Yang et al., 2013 ; Kim et al., 2016d ). Similarly, all the distinguishing crystalline peaks were shown in the S-SNEDDS ( Figure 3(B-d) ).…”

Section: Resultsmentioning

confidence: 99%

A novel solid self-nanoemulsifying drug delivery system (S-SNEDDS) for improved stability and oral bioavailability of an oily drug, 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol

et al. 2017

Self Cite

To develop a novel solid self-nanoemulsifying drug delivery system (S-SNEDDS) for a water-insoluble oily drug, 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) with improved stability and oral bioavailability, numerous S-SNEDDS were prepared with surfactant, hydrophilic polymer, antioxidant, and calcium silicate (porous carrier) using the spray-drying method. Their physicochemical properties were evaluated using emulsion droplet size analysis, SEM and PXRD. Moreover, the solubility, dissolution, stability, and pharmacokinetics of the selected S-SNEDDS were assessed compared with the drug and a commercial soft capsule. Sodium lauryl sulfate (SLS) and hydroxypropyl methylcellulose (HPMC) with the highest drug solubility were selected as surfactant and hydrophilic polymer, respectively. Among the antioxidants tested, only butylated hydroxyanisole (BHA) could completely protect the drug from oxidative degradation. The S-SNEDDS composed of PLAG/SLS/HPMC/BHA/calcium silicate at a weight ratio of 1: 0.25: 0.1: 0.0002: 0.5 provided an emulsion droplet size of less than 300 nm. In this S-SNEDDS, the drug and other ingredients might exist in the pores of carrier and attach onto its surface. It considerably improved the drug stability (about 100 vs. 70%, 60 °C for 5 d) and dissolution (about 80 vs. 20% in 60 min) compared to the commercial soft capsule. Moreover, the S-SNEDDS gave higher AUC, C, and T values than the commercial soft capsule; in particular, the former improved the oral bioavailability of PLAG by about 3-fold. Our results suggested that this S-SNEDDS provided excellent stability and oral bioavailability of PLAG. Thus, this S-SNEDDS would be recommended as a powerful oral drug delivery system for an oily drug, PLAG.

“…The SEGS had a faster time to maximum concentration (T max ) as compared with the SNEDDS; however, there were no significant differences in T max value among all formulations. The enhanced oral bioavailability of the SEGS and SNEDDS results from an increased solubility and dissolution [39,40]. Moreover, SEGS produced by fluid bed granulation gave a higher and faster oral bioavailability of the oily drug than that of the SNEDDS produced by spray-drying.…”

Section: Resultsmentioning

confidence: 99%

Comparison of 1-Palmitoyl-2-Linoleoyl-3-Acetyl-Rac-Glycerol-Loaded Self-Emulsifying Granule and Solid Self-Nanoemulsifying Drug Delivery System: Powder Property, Dissolution and Oral Bioavailability

Lim

et al. 2019

Pharmaceutics

The main objective of this study was to compare the powder property, dissolution and bioavailability of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG)-loaded self-emulsifying granule system (SEGS) and solid self-nanoemulsifying drug delivery system (SNEDDS). Various SEGS formulations were prepared, and the effect of surfactant and binder on the drug solubility in them, leading to selecting sodium lauryl sulphate (SLS) and hydroxyl propyl methyl cellulose (HPMC). The SEGS and SNEDDS were prepared with PLAG/SLS/HPMC/calcium silicate/microcrystalline cellulose at the weight ratio of 1:0.25:0.1:0.5:3 employing the fluid bed granulation and spray-drying technique, respectively. Their powder properties were compared in terms of flow ability, emulsion droplet size, scanning electron microscopy, and powder X-ray diffraction. Furthermore, the solubility, dissolution, and oral bioavailability in rats of the SEGS were assessed in comparison with the SNEDDS. The SEGS and SNEDDS enhanced the solubility of the drug approximately 36- and 32-fold as compared with the drug alone; but they had no differences. The crystalline drug may exist in both the calcium silicate and microcrystalline cellulose (MCC) in the SEGS, but only in the calcium silicate in the SNEDDS. The SEGS had considerably improved the flow ability (Hausner ratio, 1.23 vs. 1.07; Carr index, 19.8 vs. 43.5%) and drug dissolution as compared with the SNEDDS. The SEGS and SNEDDS with double peak profiles, unlike the single peak of drug alone, showed a significantly higher plasma concentration and area under the curve (AUC), as compared with drug alone. Although they were not significantly different, the SEGS gave higher AUC than did the SNEDDS, suggesting its enhanced oral bioavailability of PLAG. Thus, the SEGS could be used as a powerful oral dosage form to improve the flow ability and oral bioavailability of PLAG, an oily drug.