In vivo dissolution behavior of various RF magnetron sputtered Ca-P coatings

Schizophrenia, a psychiatric disorder, requires long-term treatment; however, large fluctuations in blood drug concentration increase the risk of adverse reactions. We prepared a long-term risperidone (RIS) implantation system that can stabilize RIS release and established in-vitro and in-vivo evaluation systems. Cumulative release, drug loading, and entrapment efficiency were used as evaluation indicators to evaluate the effects of different pore formers, polymer ratios, porogen concentrations, and oil–water ratios on a RIS implant (RIS-IM). We also built a mathematical model to identify the optimized formulation by stepwise regression. We also assessed the crystalline changes, residual solvents, solubility and stability after sterilization, in-vivo polymer degradation, pharmacokinetics, and tissue inflammation in the case of the optimized formulation. The surface of the optimized RIS microspheres was small and hollow with 134.4 ± 3.5 µm particle size, 1.60 SPAN, 46.7% ± 2.3% implant drug loading, and 93.4% entrapment efficiency. The in-vitro dissolution behavior of RIS-IM had zero-order kinetics and stable blood concentration; no lag time was released for over three months. Furthermore, the RIS-IM was not only non-irritating to tissues but also had good biocompatibility and product stability. Long-acting RIS-IMs with microspheres and film coatings can provide a new avenue for treating schizophrenia.

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Defect structures of sodium and chloride co-substituted hydroxyapatite and its osseointegration capacity

Journal of Materials Science ◽

10.1007/s10853-020-05645-9 ◽

2021 ◽

Vol 56 (9) ◽

pp. 5493-5508

Author(s):

Dong Su Yoo ◽

Jung Sang Cho ◽

Yong-Chae Chung ◽

Sang-Hoon Rhee

Keyword(s):

Binding Energies ◽

Dissolution Behavior ◽

Total System ◽

Carbonate Apatite ◽

In Vivo Test ◽

Co Substitution ◽

Constituent Elements ◽

Low Crystalline ◽

Charged Point

AbstractA defect structure and osseointegration capacity of sodium and chloride co-substituted hydroxyapatite (NaClAp) were newly studied. The NaClAp was prepared by reacting H3PO4 and Ca(OH)2 with NaNO3 and NH4Cl followed by sintering; pure hydroxyapatite (HAp) was synthesized as a control. After sintering, the co-substitution of Ca and OH with Na and Cl, respectively, produced charged point defects at Ca and PO4 sites. Also, OH molecules partially adopted a head-on structure. The calculated total system energy of NaClAp was higher, whereas the binding energies between each constituent elements and system were lower than those of HAp. These results suggest that NaClAp was less stable than HAp, due to the formation of various defects by co-substitution of Na and Cl. Indeed, NaClAp exhibited higher dissolution behavior in simulated body fluid (SBF) compared with HAp. Accordingly, this increased the capability to produce low crystalline hydroxyl carbonate apatite, likely due to the increasing degree of apatite supersaturation in SBF. Besides, the NaClAp granules showed noticeable improvements in osseointegration capacity four weeks after in vivo test compared with HAp. Collectively, these results imply that the defects made by multiple ion substitutions are useful to increase osseointegration capacity of hydroxyapatite.

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Absorption and in vivo dissolution of hydroxycholoroquine in fed subjects assessed using deconvolution techniques

British Journal of Clinical Pharmacology ◽

10.1111/j.1365-2125.1993.tb00388.x ◽

1993 ◽

Vol 36 (5) ◽

pp. 405-411 ◽

Cited By ~ 10

Author(s):

A. J. McLACHLAN ◽

S. E. TETT ◽

D. J. CUTLER ◽

R. O. DAY

Keyword(s):

Deconvolution Techniques ◽

In Vivo Dissolution

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Physiologically Relevant In Vitro-In Vivo Correlation (IVIVC) Approach for Sildenafil with Site-Dependent Dissolution

Pharmaceutics ◽

10.3390/pharmaceutics11060251 ◽

2019 ◽

Vol 11 (6) ◽

pp. 251 ◽

Cited By ~ 4

Author(s):

Tae Hwan Kim ◽

Soyoung Shin ◽

Seok Won Jeong ◽

Jong Bong Lee ◽

Beom Soo Shin

Keyword(s):

Dissolution Kinetics ◽

Immediate Release ◽

Relative Bioavailability ◽

Wet Granulation ◽

Population Pharmacokinetic ◽

Beagle Dogs ◽

Concentration Time ◽

In Vivo Dissolution

This study aimed to establish a physiologically relevant in vitro-in vivo correlation (IVIVC) model reflecting site-dependent dissolution kinetics for sildenafil based on population-pharmacokinetic (POP-PK) modeling. An immediate release (IR, 20 mg) and three sustained release (SR, 60 mg) sildenafil tablets were prepared by wet granulation method. In vitro dissolutions were determined by the paddle method at pH 1.2, 4.5, and 6.8 media. The in vivo pharmacokinetics were assessed after oral administration of the prepared IR and SR formulations to Beagle dogs (n = 12). The dissolution of sildenafil from SR formulations was incomplete at pH 6.8, which was not observed at pH 1.2 and pH 4.5. The relative bioavailability was reduced with the decrease of the dissolution rate. Moreover, secondary peaks were observed in the plasma concentration-time curves, which may result from site-dependent dissolution. Thus, a POP-PK model was developed to reflect the site-dependent dissolution by separately describing the dissolution and absorption processes, which allowed for estimation of the in vivo dissolution of sildenafil. Finally, an IVIVC was established and validated by correlating the in vitro and in vivo dissolution rates. The present approach may be applied to establish IVIVC for various drugs with complex dissolution kinetics for the development of new formulations.

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Comparison of in vivo dissolution processes in hydroxyapatite and silicon-substituted hydroxyapatite bioceramics

Biomaterials ◽

10.1016/s0142-9612(03)00355-7 ◽

2003 ◽

Vol 24 (25) ◽

pp. 4609-4620 ◽

Cited By ~ 321

Author(s):

A.E. Porter ◽

N. Patel ◽

J.N. Skepper ◽

S.M. Best ◽

W. Bonfield

Keyword(s):

In Vivo Dissolution

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Development of Level A In Vitro–Vivo Correlation for Electrosprayed Microspheres Containing Leuprolide: Physicochemical, Pharmacokinetic, and Pharmacodynamic Evaluation

Pharmaceutics ◽

10.3390/pharmaceutics12010036 ◽

2020 ◽

Vol 12 (1) ◽

pp. 36

Author(s):

Dong-Seok Lee ◽

Dong Wook Kang ◽

Go-Wun Choi ◽

Han-Gon Choi ◽

Hea-Young Cho

Keyword(s):

Plasma Concentration ◽

Prediction Error ◽

Subcutaneous Administration ◽

In Vitro Dissolution ◽

Burst Release ◽

Maximum Plasma ◽

Time Curve ◽

In Vivo Dissolution

This study optimized the preparation of electrosprayed microspheres containing leuprolide and developed an in vitro–in vivo correlation (IVIVC) model that enables mutual prediction between in vitro and in vivo dissolution. The pharmacokinetic (PK) and pharmacodynamic (PD) study of leuprolide was carried out in normal rats after subcutaneous administration of electrosprayed microspheres. The parameters of the IVIVC model were estimated by fitting the PK profile of Lucrin depot® to the release compartment of the IVIVC model, thus the in vivo dissolution was predicted from the in vitro dissolution. From this correlation, the PK profile of leuprolide was predicted from the results of in vivo dissolution. The IVIVC model was validated by estimating percent prediction error (%PE) values. Among prepared microspheres, an optimal formulation was selected using the IVIVC model. The maximum plasma concentration and the area under the plasma concentration–time curve from zero to infinity from the predicted PK profile were 4.01 ng/mL and 52.52 h·ng/mL, respectively, and from the observed PK profile were 4.14 ng/mL and 56.95 h·ng/mL, respectively. The percent prediction error values of all parameters did not exceed 15%, thus the IVIVC model satisfies the validation criteria of the Food and Drug Administration (FDA) guidance. The PK/PD evaluation suggests that the efficacy of OL5 is similar to Lucrin depot®, but the formulation was improved by reducing the initial burst release.

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