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Effect of extraction conditions on the yield and chemical properties of pectin from cocoa husks

Chan SY, Choo WS

Food Chem, 2013 Dec 15;141(4):3752-8.
PMID: 23993545 DOI: 10.1016/j.foodchem.2013.06.097

Different extraction conditions were applied to investigate the effect of temperature, extraction time and substrate-extractant ratio on pectin extraction from cocoa husks. Pectin was extracted from cocoa husks using water, citric acid at pH 2.5 or 4.0, or hydrochloric acid at pH 2.5 or 4.0. Temperature, extraction time and substrate-extractant ratio affected the yields, uronic acid contents, degrees of methylation (DM) and degrees of acetylation (DA) of the extracted pectins using the five extractants differently. The yields and uronic acid contents of the extracted pectins ranged from 3.38-7.62% to 31.19-65.20%, respectively. The DM and DA of the extracted pectins ranged from 7.17-57.86% to 1.01-3.48%, respectively. The highest yield of pectin (7.62%) was obtained using citric acid at pH 2.5 [1:25 (w/v)] at 95 °C for 3.0 h. The highest uronic acid content (65.20%) in the pectin was obtained using water [1:25 (w/v)] at 95 °C for 3.0 h.
Fulltext Detection and serotyping of dengue viruses by PCR: a simple, rapid method for the isolation of viral RNA from infected mosquito larvae

Chan SY, Kautner I, Lam SK

Southeast Asian J Trop Med Public Health, 1994 Jun;25(2):258-61.
PMID: 7855637

Dengue viruses pose a considerable global public health problem with an estimated 100 million cases of illness every year. This illustrates the need for rapid and reliable diagnostic methods for proper patient management and disease control. Currently, laboratory diagnosis depends on serology or virus isolation, with both methods having certain drawbacks. Alternatively, reverse transcription and polymerase chain reaction (RT-PCR) offers the potential for the rapid, highly sensitive and specific detection of dengue viruses. Since we occasionally encounter the problem of insufficient amounts of patient serum for the direct detection of dengue viruses, a method was developed for the extraction of viral RNA after biological amplification in mosquito larvae. Using this method, 15 of 19 clinical samples tested were correctly identified using RT-PCR.
The influence of antibody levels in dengue diagnosis by polymerase chain reaction

Chan SY, Kautner IM, Lam SK

J Virol Methods, 1994 Oct;49(3):315-22.
PMID: 7868649

The potential of RT-PCR to rapidly diagnose dengue infections from both acute and convalescent phase patients' sera was evaluated. The RNA extraction method involved binding of the viral RNA to silica particles in the presence of high concentration of guanidine thiocyanate. The protocol that was established was sensitive enough to detect 40 plaque forming units per 100 microliter of serum and results could be obtained within one day. Results from this study indicate that clinical samples should be collected in the early acute phase of illness when anti-dengue antibodies were undetectable or of low titres to ensure a more reliable diagnosis.
Cellular proteome alterations in response to enterovirus 71 and coxsackievirus A16 infections in neuronal and intestinal cell lines

Chan SY, Sam IC, Lai JK, Chan YF

J Proteomics, 2015 Jul 1;125:121-30.
PMID: 26003530 DOI: 10.1016/j.jprot.2015.05.016

Hand, foot and mouth disease is mainly caused by enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16), but EV-A71 is also associated with severe neurological complications. Host factors may contribute to the different clinical outcomes of EV-A71 and CV-A16 infections. A neurovirulent EV-A71 strain (EV-A71/UH1) from a fatal case, a non-neurovirulent EV-A71 strain (EV-A71/Sha66) and a CV-A16 strain (CV-A16/22159) from cases of uncomplicated HFMD were used. Replication of the viruses in SK-N-MC (neuronal) and HT-29 (intestinal) cell lines correlated with the severity of clinical disease associated with each virus. EV-A71/UH1 showed the greatest replication in neuronal cells. In HT-29 cells, both EV-A71 strains replicated well, but CV-A16/22159 showed no effective replication. The proteomes of mock and infected SK-N-MC and HT-29 cell lines were compared by 2D-SDS-PAGE. The differentially expressed proteins were identified by MALDI-TOF/TOF analysis. There were 46 and 44 differentially expressed proteins identified from SK-N-MC and HT-29 cells, respectively, categorized under apoptosis, stress, cytoskeletal, energy metabolism proteins and others. Western blot validation showed that EV-A71/UH1 and CV-A16 also differentially induced proteins involved in viral RNA translation and host cell stress responses in neuronal and intestinal cell lines.
Quantification of atovaquone from amorphous solid dispersion formulation using HPLC: An in vitro and ex vivo investigation

Teoh XY, Goh CF, Aminu N, Chan SY

J Pharm Biomed Anal, 2021 Jan 05;192:113631.
PMID: 33011581 DOI: 10.1016/j.jpba.2020.113631

Atovaquone (ATQ) is a poorly soluble drug. Therefore, formulating ATQ into its supersaturated state through solid dispersion for bioavailability enhancement can be of great value. However, due to fast crystallising properties of ATQ, the quantification of ATQ in a supersaturated solid dispersion system can be complicated. Therefore, in pursuit of accurate quantification of such sample, a simple HPLC analytical method utilising a C18 column (250 × 4.6 mm ID, 5 μm) for the quantitation of ATQ has been developed and validated. Atovaquone elution using the proposed method demonstrated a retention time around 7.6 min with good linearity (R2 > 0.999). The system suitability is also detailed with the tailing factor at 1.365 ± 0.002. The addition of solubilising agent as sample treatment step aided in ensuring the accurate quantitation of the fast crystallising ATQ. The developed HPLC quantitation method has been successfully employed in the analysis of ATQ from solid dispersion samples in in vitro dissolution as well as ex vivo permeation studies for formulation development.
In vitro study and structure-activity relationship analysis of stilbenoid derivatives as powerful vasorelaxants: Discovery of new lead compound

Chan SY, Loh YC, Oo CW, Yam MF

Bioorg Chem, 2020 11;104:104239.
PMID: 33142420 DOI: 10.1016/j.bioorg.2020.104239

The development of vasorelaxant as the antihypertensive drug is important as it produces a rapid and direct relaxation effect on the blood vessel muscles. Resveratrol (RV), as the most widely studied stilbenoid and the lead compound, inducing the excellent vasorelaxation effect through the multiple signalling pathways. In this study, the in vitro vascular response of the synthesized trans-stilbenoid derivatives, SB 1-8e were primarily evaluated by employing the phenylephrine (PE)-precontracted endothelium-intact isolated aortic rings. Herein we report trans-3,4,4'-trihydroxystilbene (SB 8b) exhibited surprisingly more than 2-fold improvement to the maximal relaxation (Rmax) of RV. This article also highlights the characterization of the aromatic protons in terms of their unique splitting patterns in 1H NMR.
Fulltext Thixotropic Supramolecular Pectin-Poly(Ethylene Glycol) Methacrylate (PEGMA) Hydrogels

Chan SY, Choo WS, Young DJ, Loh XJ

Polymers (Basel), 2016 Nov 18;8(11).
PMID: 30974681 DOI: 10.3390/polym8110404

Pectin is an anionic, water-soluble polymer predominantly consisting of covalently 1,4-linked α-d-galacturonic acid units. This naturally occurring, renewable and biodegradable polymer is underutilized in polymer science due to its insolubility in organic solvents, which renders conventional polymerization methods impractical. To circumvent this problem, cerium-initiated radical polymerization was utilized to graft methoxy-poly(ethylene glycol) methacrylate (mPEGMA) onto pectin in water. The copolymers were characterized by ¹H nuclear magnetic resonance (NMR), Fourier transform infrared (FTIR) spectroscopy and thermogravimetric analysis (TGA), and used in the formation of supramolecular hydrogels through the addition of α-cyclodextrin (α-CD) to induce crosslinking. These hydrogels possessed thixotropic properties; shear-thinning to liquid upon agitation but settling into gels at rest. In contrast to most of the other hydrogels produced through the use of poly(ethylene glycol) (PEG)-grafted polymers, the pectin-PEGMA/α-CD hydrogels were unaffected by temperature changes.
Fulltext Creation of Novel Antihypertensive Agent via Structure-Activity Relationship Study on Phytochemicals towards Vasorelaxant Activity

Loh YC, Chan SY, Oo CW, Yam MF

J Pharmacopuncture, 2020 Jun 30;23(2):88-89.
PMID: 32685237 DOI: 10.3831/KPI.2020.23.013
A dual-action chitosan-based nanogel system of triclosan and flurbiprofen for localised treatment of periodontitis

Aminu N, Chan SY, Yam MF, Toh SM

Int J Pharm, 2019 Oct 30;570:118659.
PMID: 31493495 DOI: 10.1016/j.ijpharm.2019.118659

This study aimed to develop a dual action, namely anti-inflammatory and antimicrobial, nanogels (NG) for the treatment of periodontitis using triclosan (TCS) and flurbiprofen (FLB). Triclosan, an antimicrobial drug, was prepared as nanoparticles (NPs) using poly-ε-caprolactone (PCL), while flurbiprofen, an anti-inflammatory drug, was directly loaded in a chitosan (CS) based hydrogel. The entwinement of both NPs and hydrogel loaded systems resulted in the NG. The characterisation data confirmed that the developed formulation consists of nanosized spherical structures and displays pH-dependent swelling/erosion and temperature-responsiveness. Besides, the NG exhibited adequate bioadhesiveness using the chicken pouch model and displayed antibacterial activity through the agar plate method. An in-vivo study of the NG on experimental periodontitis (EP) rats confirmed the dual antibacterial and anti-inflammatory effects which revealed an excellent therapeutic outcome. In conclusion, a dual action NG was successfully developed and proved to have superior therapeutic effects in comparison to physical mixtures of the individual drugs.
Pectin as a rheology modifier: Origin, structure, commercial production and rheology

Chan SY, Choo WS, Young DJ, Loh XJ

Carbohydr Polym, 2017 Apr 01;161:118-139.
PMID: 28189220 DOI: 10.1016/j.carbpol.2016.12.033

Pectins are a diverse family of biopolymers with an anionic polysaccharide backbone of α-1,4-linked d-galacturonic acids in common. They have been widely used as emulsifiers, gelling agents, glazing agents, stabilizers, and/or thickeners in food, pharmaceutical, personal care and polymer products. Commercial pectin is classified as high methoxy pectin (HMP) with a degree of methylation (DM) >50% and low methoxy pectin (LMP) with a DM <50%. Amidated low methoxy pectins (ALMP) can be obtained through aminolysis of HMP. Gelation of HMP occurs by cross-linking through hydrogen bonds and hydrophobic forces between the methyl groups, assisted by a high co-solute concentration and low pH. In contrast, gelation of LMP occurs by the formation of ionic linkages via calcium bridges between two carboxyl groups from two different chains in close proximity, known as the 'egg-box' model. Pectin gels exhibit Newtonian behaviour at low shear rates and shear-thinning behaviour when the shear rate is increased. An overview of pectin from its origin to its physicochemical properties is presented in this review.
Formulation strategy of nitrofurantoin: co-crystal or solid dispersion?

Teoh XY, Bt Mahyuddin FN, Ahmad W, Chan SY

Pharm Dev Technol, 2020 Feb;25(2):245-251.
PMID: 31690150 DOI: 10.1080/10837450.2019.1689401

Poor solubility and bioavailability of drugs are often affected by its microscopic structural properties. Nitrofurantoin (NF), a Biopharmaceutics Classification System class II item, has a low water solubility with low plasma concentrations. To improve its therapeutic efficacy, formulation strategy of solid dispersion (SD) and co-crystallization are compared herein. The co-crystal is prepared with citric acid in 1:1 stoichiometric ratio while SD consists of 30% w/w nitrofurantoin and 70% w/w hydroxypropyl methylcellulose (HPMC) as the carrier system. As a control, the physical mixture of NF and HPMC was prepared. All the preparations were characterized with differential scanning calorimetry (DSC), attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), microscopy analysis, solubility, and dissolution studies. The formation of co-crystal, solvent evaporated, and spray-dried SD are confirmed by the ATR-FTIR where peaks shifting of several functional groups indicate the formation of the hydrogen bond. Dissolution studies showed a greater initial dissolution rate in co-crystal than SD despite the possible presence of amorphous content in the SD system. Overall, co-crystal is concluded to be a better approach than SD for an effective dissolution.
Two successful deliveries of healthy children by a young woman diagnosed and treated during induction and relapsed therapy for acute promyelocytic leukemia

Dang CC, Guan YK, Lau NS, Chan SY

J Oncol Pharm Pract, 2020 Dec;26(8):2034-2037.
PMID: 32279594 DOI: 10.1177/1078155220915764

INTRODUCTION: Acute promyelocytic leukemia is an oncologic emergency. The limited cases reported in the literature have led to poor understanding of the safety of management of acute promyelocytic leukemia during pregnancy.
CASE REPORT: Herein is an acute promyelocytic leukemia case of a 22-year-old young pregnant woman who had various social problems. The patient was diagnosed with acute promyelocytic leukemia in her the second trimester of her first pregnancy.Management and outcome: She was treated with all-trans-retinoic acid with idarubicin and successfully delivered a healthy baby. She completed induction with idarubicin but defaulted her all-trans-retinoic acid, 6-mercaptopurine and methotrexate maintenance. She relapsed after one year and was salvaged with all-trans-retinoic acid high dose cytarabine and arsenic trioxide. She went into remission and had autologous stem cells collected and was planned for an autologous stem cell transplant but she defaulted. She relapsed when she was pregnant with her second baby during her third trimester (29+weeks) 10 months later. Salvage chemotherapy with arsenic trioxide, all-trans-retinoic acid and idarubicin was given. Patient underwent an emergency lower segment caesarian section at 31 weeks of pregnancy due to abnormal fetal cardiotocography. A healthy baby was delivered.
DISCUSSION: This drug regimen is controversial during pregnancy owing to the teratogenic effects and fatal retinoic acid syndrome especially in early gestation. In this case, patient was started the induction therapy of all-trans-retinoic acid treatment at her second trimester during her first pregnancy.
CONCLUSION: Our lady demonstrated the possibility of using all-trans-retinoic acid and arsenic trioxide and chemotherapy during second and third trimester with successful pregnancy outcomes.
Sustainable Dissolution Performance of a Carrier Tailored Electrospun

Teoh XY, Yeoh Y, Yoong LK, Chan SY

Pharm Res, 2020 Jan 07;37(2):28.
PMID: 31912250 DOI: 10.1007/s11095-019-2734-0

PURPOSE: This study aims to conduct an impact investigation in the hydrophobic-hydrophilic balance as an important factor for dissolution improvement of a hydrophilic carrier-based solid dispersion system.
METHODS: Polymeric carriers with different hydrophobic to hydrophilic ratios were used to prepare several electrospun solid dispersion formulations. Physicochemical properties and surface morphology of the samples were assessed using Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR), polarized light microscopy, Differential Scanning Calorimetry (DSC), X-ray Powder Diffraction (XRPD) and Scanning Electron Microscopy (SEM). Dissolution study was conducted in a non-sink condition to assess the drug release.
RESULTS: Incorporation of a higher amount of hydrophilic component showed an improvement in formulating a fully amorphous system based on XRPD, yet the dissolution rate increment showed no significant difference from the lower. Hence, the degree of crystallinity is proven not to be the crucial factor contributing to dissolution rate improvement. The presence of a concomitant hydrophobic component, however, showed ability in resisting precipitation and sustaining supersaturation.
CONCLUSION: Hydrophobicity in a binary carrier system plays an important role in achieving and maintaining the supersaturated state particularly for an amorphous solid dispersion. Graphical Abstract.
The Effect of Carrier-Drug Ratios on Dissolution Performances of Poorly Soluble Drug in Crystalline Solid Dispersion System

Liw JJ, Teoh XY, Teoh AXY, Chan SY

J Pharm Sci, 2022 Jan;111(1):95-101.
PMID: 34174289 DOI: 10.1016/j.xphs.2021.06.026

The choice of carrier and drug ratio are critical factors as far as the type of solid dispersion is concerned. Amorphous solid dispersion has been cited as the most desirable type among the different types of solid dispersion due to the benefit of amorphicity in increasing the drug solubility of a poorly soluble drug. Recent reports delineated that a partially crystalline solid dispersion system may perform better due to the inherent issue of solution mediated recrystallisation of a completely amorphous system. In oppose to the conventional choice of using amorphous polymer, this study aimed to investigate the use of a crystalline carrier, polyethylene glycol (PEG) for dissolution enhancement of a model poorly soluble drug, Flurbiprofen (FBP), a BCS Class II candidate. Solid dispersions of different FBP to PEG 6000 molar ratios via solvent evaporation were prepared. Physical characterisation of preparations was performed using differential scanning calorimetry (DSC), attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and optical microscope. DSC and ATR-FTIR analyses suggest the obtained solid dispersion exhibits crystalline FBP. This is then supported by the optical microscope analysis as the birefringence of crystals was noted. Further increasing the drug-carrier molar ratio to one-to-three and one-to-six showed that there was an amorphous FBP constituent in the system. DSC analysis revealed the melting point depression of FBP by the carrier which signifies interaction between the drug and polymer. Dissolution study showed the solid dispersion of FBP improves the drug solubility and drug release compared to the pure drug. A higher carrier ratio in the formulation results in a higher drug release.
Discovery of trans-3,4,4'-trihydroxystilbene as new lead vasorelaxant agent for antihypertensive drug development

Loh YC, Chan SY, Oo CW, Yam MF

Life Sci, 2021 Aug 01;278:119560.
PMID: 33915131 DOI: 10.1016/j.lfs.2021.119560

AIMS: The structure-vasorelaxant activity relationships (SARs) assessment in previous study has found that trans-3,4,4'-trihydroxystilbene (344OH) could potentially act as a vasorelaxing agent with demonstration of over 2-fold maximal relaxation (Rmax) compared to its analogue, resveratrol. The present study focuses on the mechanism of actions and pathways employed by 344OH and compared to its analogue to further speculate the SAR of stilbenoids towards vasorelaxation.
MATERIALS AND METHODS: The 344OH employed in present study was synthesized based on the protocol in previous study. The vascular responses towards the cumulative addition of 344OH were evaluated using in vitro rat aortic rings assays.
KEY FINDINGS: The pEC50 and Rmax values were found to be 4.33 ± 0.05 and 106 ± 3.99%, respectively. Results showed that the vasorelaxation of 344OH were predominated by G-protein-coupled muscarinic- (M3) and β2-adrenergic receptors, followed by PGI2/AC/cAMP- and NO/sGC/cGMP-dependent pathways. It was also identified that 344OH employed voltage-activated- (Kv), calcium-activated- (Kca) and inwardly-rectifying (Kir) potassium channels and act as an antagonist for both VOCC and IP3R while regulating the action potential in the vasculature.
SIGNIFICANCE: The different position of hydroxyl substituent located in A-ring of the stilbenoid backbone in 344OH compared to resveratrol resulted in a significant difference in mechanistic actions that lead to 344OH's fast-acting and less time-dependent vasorelaxation behaviour. This has substantially increased the potential of 344OH to be developed as an effective antihypertensive drug in future. Present findings further strengthen our inferences where the SARs study approach should be carried out as the mainstream methodology in future drug development research.
Recent Advances in Shape Memory Soft Materials for Biomedical Applications

Chan BQ, Low ZW, Heng SJ, Chan SY, Owh C, Loh XJ

ACS Appl Mater Interfaces, 2016 04 27;8(16):10070-87.
PMID: 27018814 DOI: 10.1021/acsami.6b01295

Shape memory polymers (SMPs) are smart and adaptive materials able to recover their shape through an external stimulus. This functionality, combined with the good biocompatibility of polymers, has garnered much interest for biomedical applications. In this review, we discuss the design considerations critical to the successful integration of SMPs for use in vivo. We also highlight recent work on three classes of SMPs: shape memory polymers and blends, shape memory polymer composites, and shape memory hydrogels. These developments open the possibility of incorporating SMPs into device design, which can lead to vast technological improvements in the biomedical field.
Fulltext The Interplay between Drug and Sorbitol Contents Determines the Mechanical and Swelling Properties of Potential Rice Starch Films for Buccal Drug Delivery

Alrimawi BH, Chan MY, Ooi XY, Chan SY, Goh CF

Polymers (Basel), 2021 Feb 15;13(4).
PMID: 33671895 DOI: 10.3390/polym13040578

Rice starch is a promising biomaterial for thin film development in buccal drug delivery, but the plasticisation and antiplasticisation phenomena from both plasticisers and drugs on the performance of rice starch films are not well understood. This study aims to elucidate the competing effects of sorbitol (plasticiser) and drug (antiplasticiser) on the physicochemical characteristics of rice starch films containing low paracetamol content. Rice starch films were prepared with different sorbitol (10, 20 and 30% w/w) and paracetamol contents (0, 1 and 2% w/w) using the film casting method and were characterised especially for drug release, swelling and mechanical properties. Sorbitol showed a typical plasticising effect on the control rice starch films by increasing film flexibility and by reducing swelling behaviour. The presence of drugs, however, modified both the mechanical and swelling properties by exerting an antiplasticisation effect. This antiplasticisation action was found to be significant at a low sorbitol level or a high drug content. FTIR investigations supported the antiplasticisation action of paracetamol through the disturbance of sorbitol-starch interactions. Despite this difference, an immediate drug release was generally obtained. This study highlights the interplay between plasticiser and drug in influencing the mechanical and swelling characteristics of rice starch films at varying concentrations.
Rice starch thin films as a potential buccal delivery system: Effect of plasticiser and drug loading on drug release profile

Chan SY, Goh CF, Lau JY, Tiew YC, Balakrishnan T

Int J Pharm, 2019 May 01;562:203-211.
PMID: 30904726 DOI: 10.1016/j.ijpharm.2019.03.044

Rice starch is known to have an excellent film-forming behaviour in the packaging industry but inadequate attention was given to this biopolymer to be developed into thin films for drug delivery. Accordingly, rice starch thin films containing a model drug, paracetamol and plasticisers (glycerol or sorbitol) were developed using film casting technique. This study focuses on investigating the impact of plasticiser and drug loading on drug release pattern of rice starch films which has not been explored to date. The obtained rice films were characterised for their physicochemical properties including swelling and dissolution study. The highest drug dissolution rate was achieved in the rice films with a low drug loading due to drug amorphicity in nature. When drug loading increases, the swelling behaviour of rice films plays a dominant role in releasing drug in the crystalline form. The role of plasticiser was indicated by the plasticiser-starch interaction where a strong interaction allows drug solubilisation more readily in the dissolution medium. It is envisaged that rice films could be tailored to achieve desired drug release pattern with different plasticiser.
New flavonoid-based compound synthesis strategy for antihypertensive drug development

Loh YC, Chan SY, Tew WY, Oo CW, Yam MF

Life Sci, 2020 May 15;249:117512.
PMID: 32145305 DOI: 10.1016/j.lfs.2020.117512

Hypertension is one of the leading causes of mortality in relation to the cardiovascular conditions and easily the most overlooked and poorly managed disease in mankind. With well over 200 drugs available in the market globally, there is still an urgency to search for antihypertensive alternatives due to the subpar efficacy and unwarranted side effects of the current choices. Present studies reported over 250 types of plant-derived compounds were being investigated for potential pharmacological effects on the vasculature in the last 3 decades. There were numerous literatures that claimed various compounds exhibiting vasorelaxant properties to a certain extent with low numbers of these compounds being successfully adapted into the current medicinal practice for treatment of hypertension. The issue is the scarcity of reviews that summarizes the discovery of this field and the lack of thorough comparison of these compounds to identify which of these vasodilators should be the next face of hypertension management. Thus, this review is aiming towards identifying the relationship between a major class of plant-derived compounds, flavonoid's activity as a vasodilator with their signalling pathways and their structural characteristics according to their vasorelaxant properties. Interestingly, we found that both nitric oxide and voltage-operated calcium channels pathways, and two of the flavonoid's structural characteristics play crucial roles in eliciting strong vasorelaxant effects. We have faith that the insights of this review will serve as a reference for those researching similar topics in the future and potentially lead to the development of more promising antihypertensive alternative.
The improved dissolution performance of a post processing treated spray-dried crystalline solid dispersion of poorly soluble drugs

Chan SY, Toh SM, Khan NH, Chung YY, Cheah XZ

Drug Dev Ind Pharm, 2016 Nov;42(11):1800-1812.
PMID: 27049232

Solution-mediated transformation has been cited as one of the main problems that deteriorate dissolution performances of solid dispersion (SD). This is mainly attributed by the recrystallization tendency of poorly soluble drug. Eventually, it will lead to extensive agglomeration which is a key process in reducing the dissolution performance of SD and offsets the true benefit of SD system. Here, a post-processing treatment is suggested in order to reduce the recrystallization tendency and hence bring forth the dissolution advantage of SD system.

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