scholarly journals Hot-Melt Extruded Amorphous Solid Dispersion for Solubility, Stability, and Bioavailability Enhancement of Telmisartan

2021 ◽  
Vol 14 (1) ◽  
pp. 73
Author(s):  
Bhupendra Raj Giri ◽  
Jaewook Kwon ◽  
Anh Q. Vo ◽  
Ajinkya M. Bhagurkar ◽  
Suresh Bandari ◽  
...  
Keyword(s):  
Solid Dispersion ◽  
Amorphous State ◽  
In Vitro Dissolution ◽  
Amorphous Solid Dispersion ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Hydrophilic Polymer ◽  
Dissolution Profile ◽  
Maximum Serum ◽  
Hot Melt

Telmisartan (TEL, an antihypertensive drug) belongs to Class II of the Biopharmaceutical Classification System (BCS) because of its poor aqueous solubility. In this study, we enhanced the solubility, bioavailability, and stability of TEL through the fabrication of TEL-loaded pH-modulated solid dispersion (TEL pHM-SD) using hot-melt extrusion (HME) technology. We prepared different TEL pHM-SD formulations by varying the ratio of the drug (TEL, 10–60% w/w), the hydrophilic polymer (Soluplus®, 30–90% w/w), and pH-modifier (sodium carbonate, 0–10% w/w). More so, the tablets prepared from an optimized formulation (F8) showed a strikingly improved in vitro dissolution profile (~30-fold) compared to the free drug tablets. The conversion of crystalline TEL to its amorphous state is observed through solid-state characterizations. During the stability study, F8 tablets had a better stability profile compared to the commercial product with F8, showing higher drug content, low moisture content, and negligible physical changes. Moreover, compared to the TEL powder, in vivo pharmacokinetic studies in rats showed superior pharmacokinetic parameters, with maximum serum concentration (Cmax) and area under the drug concentration–time curve (AUC0–∞) of the TEL pHM-SD formulation increasing by 6.61- and 5.37-fold, respectively. Collectively, the results from the current study showed that the inclusion of a hydrophilic polymer, pH modulator, and the amorphization of crystalline drugs in solid dispersion prepared by HME can be an effective strategy to improve the solubility and bioavailability of hydrophobic drugs without compromising the drug’s physical stability.

scholarly journals Developing pH-Modulated Spray Dried Amorphous Solid Dispersion of Candesartan Cilexetil with Enhanced In Vitro and In Vivo Performance

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 497
Author(s):  
Surendra Poudel ◽  
Dong Wuk Kim
Keyword(s):  
Solid Dispersion ◽  
Oral Absorption ◽  
Candesartan Cilexetil ◽  
Amorphous State ◽  
Amorphous Solid ◽  
In Vitro Dissolution ◽  
Amorphous Solid Dispersion ◽  
Pharmacokinetic Parameters ◽  
Highly Effective

Candesartan cilexetil (CC), a prodrug and highly effective antihypertensive agent, is a poorly soluble (BCS Class II) drug with limited bioavailability. Here, we attempted to improve CC’s bioavailability by formulating several CC-loaded amorphous solid dispersions with a hydrophilic carrier (PVPK30) and pH modifier (sodium carbonate) using the spray drying technique. Solubility, in vitro dissolution, and moisture content tests were used for screening the optimized formulation. We identified an optimized formulation of CC/PVPK30/SC, which at the ratio of 1:0.5:1 (w/w/w) exhibited a 30,000-fold increase in solubility and a more than 9-fold enhancement in dissolution compared to pure CC. Solid-state characterization revealed that in pH-modulated CC amorphous solid dispersion (CCSDpM), CC’s crystallinity was altered to an amorphous state with the absence of undesirable interactions. Stability studies also showed that the optimized formulation was stable with good drug content and drug release under accelerated conditions of up to 4 weeks and real-time stability conditions of up to 12 weeks. Furthermore, pharmacokinetic parameters, such as AUC and Cmax of candesartan, had a 4.45-fold and 7.42-fold improvement, respectively, in CCSDpM-treated rats compared to those in the CC-treated rats. Thus, these results suggest that CCSDpM is highly effective for increasing oral absorption. The application of these techniques can be a viable strategy to improve a drug’s bioavailability.

Fenofibrate Solid Dispersion Processed by Hot-Melt Extrusion: Elevated Bioavailability and Its Cell Transport Mechanism

2019 ◽  
Vol 16 (6) ◽  
pp. 538-547 ◽  
Author(s):  
Ting Wen ◽  
Boyi Niu ◽  
Qiaoli Wu ◽  
Yixian Zhou ◽  
Xin Pan ◽  
...  
Keyword(s):  
Solid Dispersion ◽  
Amorphous Solid ◽  
Hot Melt Extrusion ◽  
In Vitro Dissolution ◽  
Amorphous Solid Dispersion ◽  
Dissolution Test ◽  
Melt Extrusion ◽  
Cell Transport ◽  
Hot Melt

Background: Fenofibrate (FNB) is an effective drug for the treatment of hypertriglyceridemia, hypercholesterolemia as well as mixed hyperlipidemia. However, due to its poor aqueous solubility, FNB has the problem of poor oral absorption followed by low bioavailability. Objective: The aim of this research was to construct FNB amorphous solid dispersion employing PVP VA64 as the carrier by hot-melt extrusion method, in order to improve the oral bioavailability. Additionally, the cell transport experiment was conducted to further investigate the mechanism of promoted osmotic absorption. Methods: The physical state of the obtained solid dispersion was characterized using SEM, DSC and XRD. Besides, in vitro Caco-2 cells were used to evaluate the cytotoxicity of the carrier and mimic gastrointestinal drug permeation. At last, in vitro dissolution test and in vivo bioavailability study were also carried out. Results: The prepared FNB solid dispersion was found to be an amorphous state after hot-melt extrusion process. In vitro cytotoxicity test on Caco-2 cells confirmed the excellent biocompatibility of the carrier PVP VA64. Besides, transwell cell transport assay and in vitro dissolution test revealed that FNB released from amorphous solid dispersion was equipped with an improved transmembrane transport and dissolution rate. Moreover, pharmacokinetic study in beagle dogs showed that comparing with commercial micronized product Lipanthyl®, the oral bioavailability of FNB solid dispersion was significantly enhanced (2.45 fold). Conclusion: In conclusion, PVP VA64 can be regarded as a promising polymer to enhance the bioavailability of poorly water-soluble drugs such as FNB processed by hot-melt extrusion. Besides, investigations on the mechanism of the enhanced penetration are expected to lay a foundation on the subsequent development of effective and practical solid dispersion.

scholarly journals FABRICATION AND EVALUATION OF SOLID DISPERSION CONTAINING GLIBENCLAMIDE

2018 ◽  
Vol 11 (8) ◽  
pp. 158
Author(s):  
Nikita Sehgal ◽  
Vishal Gupta N ◽  
Gowda Dv ◽  
Sivadasu P
Keyword(s):  
Dissolution Rate ◽  
Solid Dispersion ◽  
Solid Dispersions ◽  
Amorphous State ◽  
In Vitro Dissolution ◽  
Dissolution Profile ◽  
Stability Studies ◽  
Scanning Calorimetry ◽  
Dsc Studies

 Objective: The aim of the present study was to increase the dissolution rate of glibenclamide (GLIB) by molecular dispersion of drug in the polymeric matrix of Pluronic F-127.Methods: GLIB-loaded solid dispersions were formulated by fusion method. The formulated solid dispersions were characterized for scanning electron microscopy (SEM), X-ray diffractometry (XRD), differential scanning calorimetry (DSC), and evaluated for percentage yield, drug content, solubility, and in vitro dissolution profile, and stability studies were conducted as per International Conference on Harmonisation guidelines Q1A in stability chamber, both at intermediate and accelerated conditions.Results: Both XRD and DSC studies suggested that crystalline GLIB was converted to amorphous form after loading into carrier. SEM studies revealed that the prepared solid dispersions were in the form of irregular particles with the absence of crystalline material. Due to this conversion of crystalline to amorphous state, formulated solid dispersions had shown improved dissolution rate profile of GLIB and stability studies suggested that formulated solid dispersions showed no significant changes in appearance and also in drug content.Conclusion: Thus, from the obtained results, it can be concluded that dissolution profile of GLIB can be improved by formulating as solid dispersion.

scholarly journals Artemether-Soluplus Hot-Melt Extrudate Solid Dispersion Systems for Solubility and Dissolution Rate Enhancement with Amorphous State Characteristics

2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Ritesh A. Fule ◽  
Tarique S. Meer ◽  
Ajay R. Sav ◽  
Purnima D. Amin
Keyword(s):  
Dissolution Rate ◽  
Solid Dispersion ◽  
Amorphous State ◽  
Polymer Melt ◽  
Aqueous Solubility ◽  
Dissolution Profile ◽  
Scanning Calorimetry ◽  
Peg 400 ◽  
Hot Melt

This work studied artemether (ARTM) solid dispersion (SD) formulation using mixture of polymer excipient Soluplus, PEG 400, Lutrol F127, and Lutrol F68 melts at temperatures lower than the melting point of ARTM using a laboratory-size, single-screw rotating batch extruder. The effects of three surfactants PEG 400, Lutrol F127, and Lutrol F68 and parameters like mixing temperature, screw rotating speed, and residence time were systematically studied. SEM, XRD, and FT-IR were employed to investigate the evolution of ARTM’s dissolution into the molten excipient. Differential scanning calorimetry (DSC) was used to quantitatively study the melting enthalpy evolution of the drug. The results showed that the dissolution rate increased with increasing the ratio of polymer and surfactant to that of drug. It was concluded that the dissolution of the drug in the polymer melt is a convective diffusion process and that laminar distributive mixing can significantly enhance the dissolution rate. The aqueous solubility and dissolution rate of prepared solid dispersion were significantly enhanced. In vitro antimalarial studies revealed marked improvement in IC50 values. Thus hot-melt extrusion (HME) is a promising technology for improving solubility and dissolution profile of ARTM.

scholarly journals Influence of Drug Load on the Printability and Solid-State Properties of 3D-Printed Naproxen-Based Amorphous Solid Dispersion

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4492
Author(s):  
Eric Ofosu Kissi ◽  
Robin Nilsson ◽  
Liebert Parreiras Nogueira ◽  
Anette Larsson ◽  
Ingunn Tho
Keyword(s):  
Solid State ◽  
3D Printing ◽  
Solid Dispersion ◽  
Physical Stability ◽  
Amorphous Solid ◽  
Amorphous Solid Dispersion ◽  
Drug Load ◽  
X Ray ◽  
3D Printed ◽  
Hot Melt

Fused deposition modelling-based 3D printing of pharmaceutical products is facing challenges like brittleness and printability of the drug-loaded hot-melt extruded filament feedstock and stabilization of the solid-state form of the drug in the final product. The aim of this study was to investigate the influence of the drug load on printability and physical stability. The poor glass former naproxen (NAP) was hot-melt extruded with Kollidon® VA 64 at 10–30% w/w drug load. The extrudates (filaments) were characterised using differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), and thermogravimetric analysis (TGA). It was confirmed that an amorphous solid dispersion was formed. A temperature profile was developed based on the results from TGA, DSC, and DMA and temperatures used for 3D printing were selected from the profile. The 3D-printed tablets were characterised using DSC, X-ray computer microtomography (XµCT), and X-ray powder diffraction (XRPD). From the DSC and XRPD analysis, it was found that the drug in the 3D-printed tablets (20 and 30% NAP) was amorphous and remained amorphous after 23 weeks of storage (room temperature (RT), 37% relative humidity (RH)). This shows that adjusting the drug ratio can modulate the brittleness and improve printability without compromising the physical stability of the amorphous solid dispersion.

scholarly journals The Development and Optimization of Hot-Melt Extruded Amorphous Solid Dispersions Containing Rivaroxaban in Combination with Polymers

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 344
Author(s):  
Jong-Hwa Lee ◽  
Hyeong Sik Jeong ◽  
Jong-Woo Jeong ◽  
Tae-Sung Koo ◽  
Do-Kyun Kim ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Dissolution Rate ◽  
Solid Dispersion ◽  
Oral Drug Delivery ◽  
Amorphous Solid ◽  
Drug Dissolution ◽  
Oral Drug ◽  
Amorphous Solid Dispersion ◽  
Screw Speed ◽  
Hot Melt

Rivaroxaban (RXB), a novel oral anticoagulant that directly inhibits factor Xa, is a poorly soluble drug belonging to Biopharmaceutics Classification System (BCS) class II. In this study, a hot-melt extruded amorphous solid dispersion (HME-ASD) containing RXB is prepared by changing the drug:polymer ratio (Polyvinylpyrrolidione-vinyl acetate 64, 1:1–1:4) and barrel temperature (200–240 °C), fixed at 20% of Cremophor® RH 40 and 15 rpm of the screw speed, using the hot-melt extruding technique. This study evaluates the solubility, dissolution behavior, and bioavailability for application to oral drug delivery and optimizes the formulation of rivaroxaban amorphous solid dispersion (RXB-ASD). Based on a central composite design, optimized RXB-ASD (PVP VA 64 ratio 1:4.1, barrel temperature 216.1 °C, Cremophor® RH 40 20%, screw speed 15 rpm) showed satisfactory results for dependent variables. An in vitro drug dissolution study exhibited relatively high dissolution in four media and achieved around an 80% cumulative drug release in 120 min. Optimized RXB-ASD was stable under the accelerated condition for three months without a change in crystallinity and the dissolution rate. A pharmacokinetic study of RXB-ASD in rats showed that the absorption was markedly increased in terms of rate and amount, i.e., the systemic exposure values, compared to raw RXB powder. These results showed the application of quality by design (QbD) in the formulation development of hot-melt extruded RXB-ASD, which can be used as an oral drug delivery system by increasing the dissolution rate and bioavailability.

scholarly journals Enrichment of aqueous solubility and dissolution profile of mesalamine: In vitro evaluation of solid dispersion

2021 ◽  
Vol 9 (2) ◽  
pp. 127-135
Author(s):  
Anil Raosaheb Pawar ◽  
Pralhad Vitthalrao Mundhe ◽  
Vinayak Kashinath Deshmukh ◽  
Ramdas Bhanudas Pandhare ◽  
Tanaji Dilip Nandgude
Keyword(s):  
Ulcerative Colitis ◽  
Drug Release ◽  
Dissolution Rate ◽  
Solid Dispersion ◽  
Solid Dispersions ◽  
Aqueous Solubility ◽  
In Vitro Dissolution ◽  
Dissolution Profile ◽  
Peg 4000

The aim of the present study was to formulate solid dispersion (SD) of Mesalamine to enrich the aqueous solubility and dissolution rate. Mesalamine is used in the management of acute ulcerative colitis and for the prevention of relapse of active ulcerative colitis. In the present study, Solid dispersion of Mesalamine was prepared by Fusion and Solvent evaporation method with different polymers. SD’s were characterized by % practical yield, drug content, Solubility, FT-IR, PXRD (Powder X- ray diffractometry), SEM (Scanning electron microscopy), in vitro dissolution studies and Stability studies. The percent drug release of prepared solid dispersion of Mesalamine by fusion and solid dispersion method (FM47, FM67, SE47 and SE67) in 1:7 ratio was found 81.36±0.41, 86.29±0.64, 82.45±0.57and 87.25±1.14 respectively. The aqueous solubility and percent drug release of solid dispersion of Mesalamine by both methods was significantly increased. The PXRD demonstrated that there was a significant decrease in crystallinity of pure drug present in the solid dispersions, which resulted in an increased aqueous solubility and dissolution rate of Mesalamine.The significant increase in aqueous solubility and dissolution rate of Mesalamine was observed in solid dispersion as the crystallinity of the drug decreased, absence of aggregation and agglomeration, increased wetability and good dispersibility after addition of PEG 4000 and PEG 6000.

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