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Jung Suk Kim,1,* Fakhar ud Din,2,* Sang Min Lee,1,* Dong Shik Kim,1 Mi Ran Woo,1 Seunghyun Cheon,1 Sang Hun Ji,1 Jong Oh Kim,3 Yu Seok Youn,4 Kyung Taek Oh,5 Soo-Jeong Lim,6 Sung Giu Jin,7 Han-Gon Choi1 1College of Pharmacy, Hanyang University, Ansan, South Korea; 2Department of Pharmacy, Quaid-I-Azam University, Islamabad, Pakistan; 3College of Pharmacy, Yeungnam University, Gyongsan, South Korea; 4School of Pharmacy, Sungkyunkwan University, Suwon, South Korea; 5College of Pharmacy, Chung-Ang University, Seoul, South Korea; 6Department of Bioscience and biotechnology, Sejong University, Seoul, South Korea; 7Department of Pharmaceutical Engineering, Dankook University, Cheonan, South Korea*These authors contributed equally to this workCorrespondence: Sung Giu Jin; Han-Gon Choi Tel +82 41-550-3558; +82 31-400-5802Fax +82 41-559-7945; +82 31-400-5958Email sklover777@dankook.ac.kr; hangon@hanyang.ac.krBackground: The purpose of this study was to screen various drug delivery systems for improving the aqueous solubility and oral bioavailability of sildenafil. Three representative techniques, solid self-nanoemulsifying drug delivery systems (SNEDDS), amorphous microspheres and crystalline microspheres, were compared.Methods: Both microspheres systems contained sildenafil:Labrasol:PVP at a weight ratio of 1:1:6. The amorphous microspheres were manufactured using ethanol, while crystalline microspheres were generated using distilled water. Liquid SNEDDS was composed of sildenafil:Labrasol:Transcutol HP:Captex 300 in the ratio of 1:70:15:15 (w:w:w:w). The solidification process in SNEDDS was performed using HDK N20 Pharma as a solid carrier.Results: The amorphous microspheres appeared spherical with significantly decreased particle size compared to the drug powder. The crystalline microspheres exhibited a rough surface with no major particle-size difference compared with sildenafil powder, indicating that the hydrophilic excipients adhered to the sildenafil crystal. Solid SNEDDS presented a smooth surface, assuming that the oily liquid was adsorbed to the porous solid carrier. According to the physicochemical evaluation, the crystalline state maintained in crystalline microspheres, whereas the crystal state changed to amorphous state in other formulations. Amorphous microspheres, crystalline microspheres and solid SNEDDS produced about 79, 55, 82-fold increased solubility, compared to drug powder. Moreover, the prepared formulations provided a higher dissolution rate (%) and plasma concentration than did the drug powder (performance order; solid SNEDDS ≥ amorphous microspheres ≥ crystalline microspheres > drug powder). Among the formulations, solid SNEDDS demonstrated the highest improvement in oral bioavailability (AUC; 1508.78 ± 343.95 h·ng/mL).Conclusion: Therefore, solid SNEDDS could be recommended as an oral dosage form for enhancing the oral bioavailability of sildenafil.Keywords: sildenafil, amorphous microspheres, crystalline microspheres, solid self-nanoemulsifying drug delivery system, aqueous microenvironment, oral bioavailability

Orthodontic facemask is an extraoral orthodontic appliance used in children with skeletal Class III malocclusion to influence the maxillary and mandibular developments in a favorable direction. While the use of facemask is the most effective in patients before the growth peak, skin irritation is often observed during the treatment. Thus, the present retrospective study aimed to investigate the prevalence and pattern of such skin changes and distinguish the possible factors associated with them. Patient age and sex; orthodontic parameters, expressing the severity of malocclusion; the presence of complaints in the temporomandibular joint (TMJ) areas; and the level of patient cooperation were evaluated. Additionally, in patients with skin reactions the severity and onset time were further analyzed. The results indicated that 43.5% of the patients experienced skin changes, which were characteristic for irritant contact dermatitis. The presence of TMJ complaints, and female sex were found to have a statistically significant correlation with the occurrence of skin irritation. Furthermore, skin irritation was observed more frequently in younger patients. Clinicians should give a particular attention to the skin areas, which come in contact with the appliance at every visit in order to detect any potential problems. Moreover, patients and parents should be provided with sufficient information, regarding the possibility, prevention and management of skin problems during facemask therapy.

The purpose of the present study was to develop hydroxypropyl-β-cyclodextrin (HP-β-CD)-based solid dispersed granules as a superior system to solid dispersion. The solid dispersed granules and solid dispersion were compared in terms of powder property improvement, solubility increment and oral bioavailability enhancement of poorly water-soluble dexibuprofen. Solid dispersion (drug/HP-β-CD/Tween80 = 1:7:0.1, weight ratio) and solid dispersed granules (drug/HP-β-CD/Tween80/Microcrystalline cellulose = 1:7:0.1:4) were fabricated using a spray-dryer and fluid bed granulator, respectively. The HP-β-CD-based solid dispersed granules significantly improved solubility, dissolution profile and oral bioavailability of dexibuprofen compared to pure drug powder. Moreover, the solid dispersed granules maximised the oral bioavailability of dexibuprofen to the same extent as the solid dispersion. However, considerable improvements of powder and tablet properties were observed in solid dispersed granules as compared with solid dispersion. Therefore, HP-β-CD-based solid dispersed granules would be a prospective alternative to solid dispersion.

This study aimed to develop a Lactobacillus plantarum (L. plantarum)-loaded dual-layer wound dressing (DLD) with excellent wound recovery and mechanical properties. L. plantarum-loaded DLD was fabricated by covering the hydrogel (inner layer) with a hydrocolloid (external layer). The hydrocolloid was manufactured by the hot-melt method, consisting of liquid paraffin, polyisobutylene, styrene-isoprene-styrene, and sodium carboxymethylcellulose (12:20:25:43, w/w/w/w). In contrast, the hydrogel was fabricated by the freeze-and-thaw method to load heat-labile L. plantarum. Various non-ionic materials have been investigated to select appropriate hydrogel components. The hydrogel composed of L. plantarum stock solution, guar gum, and polyvinyl alcohol (10:2:10, w/w/w) was chosen for its excellent swelling capacity and mechanical properties. As a result, heat-labile L. plantarum was successfully loaded into the guar-gum-based DLD. Moreover, guar gum-based DLD containing L. plantarum exhibited significantly enhanced swelling capacity and elasticity compared to single hydrogel layer (swelling capacity: DLD, 920.7 ± 32.4 % vs. hydrogel, 282.2 ± 6.5 %; elastic modulus: DLD, 2.9 ± 0.3 × 10

To compare clinical and radiological outcomes and failure rates between anatomical and high femoral tunnels in remnant-preserving single-bundle posterior cruciate ligament (PCL) reconstruction. 63 patients who underwent remnant-preserving single-bundle PCL reconstruction between 2011 and 2018 with a minimum 2-year follow-up were retrospectively reviewed. Patients were divided into two groups according to the femoral tunnel position: group A (33 patients with anatomical femoral tunnel) and group H (30 patients with high femoral tunnels). The femoral tunnel was positioned at the center (group A) or upper margin (group H) of the remnant anterolateral bundle. The position of the femoral tunnel was evaluated using the grid method on three-dimensional computed tomography. Clinical and radiological outcomes and failure rates were compared between the groups at the 2-year follow-up. The position of the femoral tunnel was significantly high in group H than in group A (87.4% ± 4.2% versus 76.1% ± 3.7%, p

PURPOSE This study was performed to analyze the effect of anterior bone plug positioning on clinical and radiological outcomes in patients undergoing medial meniscus allograft transplantation (M-MAT) following anterior cruciate ligament reconstruction (ACLR). METHODS Data from 24 patients who underwent M-MAT following meniscectomy and ACLR from November 2008 to June 2017 were retrospectively investigated. Patients were divided into either the centrally positioned group (group C) or the medially positioned group (group M) based on the location of the anterior bone plug for M-MAT. Clinical and radiographic follow-up was performed at two years postoperatively. International Cartilage Repair Society (ICRS) grades of chondral lesion, graft extrusion, and meniscus signal intensity were evaluated by magnetic resonance imaging (MRI) at one year postoperatively. RESULTS There were no significant differences in demographics including follow-up time of two years between the two groups. There were no significant differences in postoperative subjective International Knee Documentation Committee (IKDC), Lysholm, and Tegner scores between groups. Furthermore, there were no significant differences in osteoarthritis progression or ICRS grade on MRI. However, group C showed significantly less absolute graft extrusion (P = .008) and relative graft extrusion (P

Aim To examine a hypothetical model of physical activity and health outcomes (cardiovascular risk and quality of life) based on the information–motivation–behavioural skills model in adults. Design A cross‐sectional survey. Methods A total of 165 adults with osteoarthritis at risk for metabolic syndrome were recruited between October 2016 and September 2017 from the outpatient clinic in South Korea. Data were collected on the model constructs such as cognitive function, social support, depressive symptoms, barriers to self‐efficacy, physical activity and quality of life. A hypothetical model was tested using the AMOS 25.0 program. Results Cognitive function and barriers to self‐efficacy had a direct effect on physical activity. Physical activity had a direct effect on cardiovascular risk, while social support and depressive symptoms had a direct effect on quality of life. Conclusions The information–motivation–behavioural skills model can predict physical activity and, in turn, cardiovascular risk and quality of life in adults with osteoarthritis at risk for metabolic syndrome.

In this study, a novel hybrid bilayer wound dressing (HBD) has been developed for delivering a thermally unstable probiotic, Lactobacillus brevis. The HBD was composed of two layer, a hydrocolloid layer and a Lactobacillus brevis-loaded hydrogel layer as a block supporter and drug carrier, respectively. Moreover, various probiotic-loaded hydrogel layers in HBD were prepared with polyvinyl alcohol (PVA) and numerous hydrophilic polymers via a freezing and thawing method, and their mechanical property, release and wound recovery were assessed. Among the hydrophilic polymers investigated, copovidone most improved the mechanical strength, swelling ability, and release properties; and thus, copovidone/PVA (ratio of 1.0/10) was determined as an appropriate composition of hydrogel layer in HBD. The selected HBD exhibited superior stability than conventional dressing, maintaining approximately 90% of Lactobacillus brevis (9.0 × 10

Purpose: The objective of this study was to exploit a novel methotrexate (MTX)-loaded solid self-microemulsifying drug delivery system (SMEDDS) with enhanced bioavailability and photostability. Materials and methods: The optimized liquid SMEDDS was composed of castor oil, Tween® 80, and Plurol® diisostearique at a voluminous ratio of 27:63:10. The solid SMEDDS was formulated by spray drying liquid SMEDDS with the solid carrier (calcium silicate). Particle size analyzer, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared (FTIR) spectroscopy experiments characterized the physiochemical properties of the MTX-loaded solid SMEDDS. These properties include a z-average diameter of emulsion around 127 nm and the amorphous form of the solid SMEDDS. Furthermore, their solubility, dissolution, and pharmacokinetics in Sprague-Dawley rats were analyzed in comparison with the MTX powder. Results: The final dissolution rate and required time for complete release of solid SMEDDS were 1.9-fold higher and 10 min shorter, respectively, than those of MTX powder. Pharmacokinetic analysis demonstrated 2.04- and 3.41-fold increments in AUC and Cmax, respectively in comparison to MTX powder. The AUC and Cmax were significantly increased in solid SMEDDS. Finally, the photostability studies revealed the substantially enhanced photostability of the MTX-loaded SMEDDS under the forced degradation and confirmatory conditions. Conclusion: This solid SMEDDS formulation could be an outstanding candidate for improving the oral bioavailability and photostability of MTX.

Bilateral chylothorax due to blunt trauma is extremely rare. We report a 74-year-old patient that developed delayed bilateral chylothorax after falling off a ladder. The patient had a simple 12th rib fracture and T12 lamina fracture. All other findings seemed normal. He was sent home and on the 5th day visited our emergency center at Halla Hospital with symptoms of dyspnea and lower back pain. Computer tomography of his chest presented massive fluid collection in his right pleural cavity and moderate amounts in his left pleural cavity with 12th rib fracture and T11-12 intervertebral space widening with bilateral facet fractures. Chest tubes were placed bilaterally and chylothorax through both chest tubes was discovered. Conservative treatment for 2 weeks failed, and thus, thoracic duct ligation was done by video assisted thoracoscopic surgery. Thoracic duct embolization was not an option. Postoperatively, the patient is now doing well and happy with the results. Early surgical treatment must be considered in the old patient, whom large amounts of chylothorax are present.

This study examined the psychometric properties of the Korean version of the Patient Knowledge Questionnaire-Osteoarthritis (PKQ-OA-K). A cross-sectional survey was conducted with 157 adults with osteoarthritis from the outpatient clinic at a university hospital in Korea. The overall correct answer rate for the PKQ-OA-K was 60.4%; notably, the drug therapy subscale had the lowest median score percentage (42.9%). For structural validity, exploratory factor analysis identified the PKQ-OA-K as two-dimensional, explaining 52.4% of the total variance. Confirmatory factor analysis showed that the two-factor model adequately fit the data. The PKQ-OA-K was positively correlated with education level ( r = 0.24) and osteoarthritis outcomes ( r = 0.17), thus verifying the hypotheses of construct validity. The intraclass correlation coefficient for test-retest reliability was 0.52; alpha was 0.44. The PKQ-OA-K has excellent validity but imperfect reliability for adults with osteoarthritis. This study recommends cautious use of the PKQ-OA-K to assess Korean patients’ knowledge of osteoarthritis.

Low aqueous solubility and poor bioavailability are major concerns in the development of oral solid-dosage drug forms. In this study, we fabricated surface-attached solid dispersion (SASD) to enhance the solubility, bioavailability, and photostability of methotrexate (MTX), a highly lipophilic and photo-unstable drug. Several MTX-loaded SASD formulations were developed for spray-drying using water as the solvent, and were investigated for their aqueous solubility and dissolution kinetics. An optimized ternary SASD formulation composed of MTX/ sodium carboxymethyl cellulose (Na˗CMC)/ sodium lauryl sulfate (SLS) at 3/0.5/0.5 (w/w) had 31.78-fold and 1.88-fold higher solubility and dissolution, respectively, than MTX powder. For SASD, the in vivo pharmacokinetic parameters AUC and Cmax were 2.90- and 3.41-fold higher, respectively, than for the MTX powder. Solid-state characterizations by differential scanning calorimetry and X-ray diffraction revealed that MTX exists in its crystalline state within the spray-dried SASD. The MTX-loaded SASD formulation showed few physical changes with photostability testing. Overall, the results indicate that the spray-dried MTX-loaded SASD formulation without organic solvents enhances the solubility and oral bioavailability of MTX without a significant deterioration of its photochemical stability.

In this study, a solidified self-nanoemulsifying drug delivery system (solidified SNEDDS) and surface-modified microspheres were developed for enhancing the oral bioavailability of carvedilol. Based on the aqueous solubility test, liquid SNEDDS was composed of Peceol™ (oil), Tween® 80 (surfactant), and Labrasol® (co-surfactant) at a weight ratio of 25/50/25, generating the smallest nanoemulsion droplet size. Then, carvedilol was added to liquid SNEDDS and spray-dried with Aerosil® to fabricate the solidified SNEDDS. Surface-modified microspheres were manufactured using copovidone (polymer) and Tween® 80 (surfactant) according to aqueous solubility test results. The proper ratio of copovidone and Tween® 80 was determined based on the solubility and dissolution test. Both prepared formulations and carvedilol powder were compared using four different criteria: physicochemical characteristics, solubility, dissolution, and oral bioavailability. For solidified SNEDDS, carvedilol was encapsulated in liquid SNEDDS and absorbed to the Aerosil® surface, leading to the conversion from a crystalline to an amorphous state. However, the drug maintained its crystal form in the surface-modified microspheres. Round and even-sized particles were attached to the rough surfaces of drug, suggesting that hydrophilic carriers adhered to the hydrophobic drug. All formulations significantly improved drug solubility, dissolution, plasma concentrations, Cmax, and AUC compared to carvedilol powder. The parameters were ranked in the following order: solidified SNEDDS > surface-modified microspheres > carvedilol powder. As a result, different solubility-increasing mechanisms provided differences in performance. For carvedilol, the formation of a nano-emulsion in solidified SNEDDS resulted in an efficient supersaturated state, leading to improved solubility (~6.1 fold), dissolution (~1.8 fold), and oral bioavailability (~1.4 fold) that was superior to the hydrophilic microenvironment in surface-modified microspheres.

The orbital complications of endoscopic sinus surgery, including diplopia and ocular motility restriction, are mainly caused by direct injury to the orbital structures. These complications are rare, but can have catastrophic consequences. Symptoms occur immediately after surgery in most cases. The authors encountered an unusual case of delayed ocular motility restriction after endoscopic sinus surgery in a patient with old medial wall fracture, without direct orbital injury during the procedure. A 77-year-old man with an old medial wall fracture of the right orbit underwent endoscopic sinus surgery for chronic pansinusitis. He complained mild diplopia on right lateral gaze after 2 weeks, which gradually worsened. After 2 months, he exhibited severe lateral gaze movement impairment in the right eye and finally underwent surgical exploration. His symptoms improved after adhesiolysis of the overgrown ethmoid sinus mucosa and periorbital tissue. The authors reported this unusual case and discussed the possible mechanism underlying ocular motility restriction.

The purpose of this study was to compare two types of emulsification techniques in a solid self-nanoemulsifying drug delivery system (SNEDDS); high-pressure homogenisation (HPH) and Shirasu porous glass membrane (SPG). Those two emulsification processes enhanced the solubility, dissolution and oral bioavailability of poorly water-soluble sildenafil base (SB) by producing fine and well-dispersed nanoemulsion droplet. The liquid SNEDDS consisting of Labrasol/Transcutol HP/coconut oil at the weight of 72/18/10, gave the smallest emulsion droplet size among the prepared liquid SNEDDS formulations. Then, the SB-loaded liquid SNEDDS was dissolved in the deionised water and applied to HPH or SPG techniques. Aerosil 200 was suspended as a mesoporous carrier and spray-dried, producing an SB-loaded solid SNEDDS. The emulsion droplet size, solubility and dissolution of each emulsification process were compared to the solid SNEDDS fabricated without any treatment of additional emulsification. Moreover, the physicochemical properties of all formulations were compared. The crystalline state of the drug in all products was converted to the amorphous state. The solid SNEDDS, subjected to HPH technique, provided fine and well-dispersed nanoemulsion. Additionally, it increasingly improved the drug solubility and dissolution as compared to the others, including SB powder, non-treated (NT) and SPG. Furthermore, it gave improved Cmax and increased AUC compared to SB powder and SPG, indicating HPH enhanced the oral bioavailability of SB the most. Thus, this solid SNEDDS with HPH would be strongly suggested as an oral SB-loaded pharmaceutical product.

A series of hydrogels with intrinsic antifouling properties was prepared via surface-functionalization of poly(2-hydroxyethyl methacrylate) [p(HEMA)]-based hydrogels with the biomembrane-mimicking zwitterionic polymer, poly(2-methacryloyloxyethyl phosphorylcholine) [p(MPC)]. The p(MPC)-modified hydrogels have enhanced surface wettability, high water content retention (61.0%&ndash, 68.3%), and good transmittance (&gt, 90%). Notably, the presence of zwitterionic MPC moieties at the hydrogel surfaces lowered the adsorption of proteins such as lysozyme and bovine serum albumin (BSA) by 73%&ndash, 74% and 59%&ndash, 66%, respectively, and reduced bacterial adsorption by approximately 10%&ndash, 73% relative to the unmodified control. The anti-biofouling properties of the p(MPC)-functionalized hydrogels are largely attributed to the dense hydration layer formed at the hydrogel surfaces by the zwitterionic moieties. Overall, the results demonstrate that biocompatible and antifouling hydrogels based on p(HEMA)-p(MPC) structures have promising potential for application in biomedical materials.

This study aimed to compare high-pressure homogenization (HPH) and Shirasu porous glass (SPG) membrane emulsification for enhancing the oral bioavailability of rivaroxaban using a self-nanoemulsifying drug delivery system (SNEDDS). The effects of two different solidifying agents (calcium silicate and colloidal silica), used in SNEDDS, on the nanoemulsion system were investigated. Liquid SNEDDS comprised 30/25/45 (w/w/w) Peceol/TPGS/Solutol HS15. The optimised HPH conditions were 1500 bar with one cycle. The SPG emulsifying time and agitation speed were set at 30 min and 100 rpm, respectively. Three different liquid SNEDDS formulations (untreated, HPH, and SPG membrane emulsified) were suspended with calcium silicate and colloidal silica and spray-dried to fabricate six solid SNEDDS formulations. The crystalline state of the drug changed to an amorphous state in all SNEDDS. The formulations solidified with calcium silicate had a finer droplet size and higher aqueous solubility than those solidified with colloidal silica. Comparing two techniques, HPH exhibited a superior nanoemulsion property, aqueous solubility and dissolution rate (%) to SPG membrane emulsification. Therefore, high-pressure homogenised SNEDDS solidified with calcium silicate was selected as the appropriate solid SNEDDS. Subsequently, an in vivo study was performed using a rat model, and the selected solid SNEDDS significantly enhanced the oral bioavailability of rivaroxaban than that of the pure drug powder. In conclusion, HPH and calcium silicate are suitable emulsifying techniques and solidifying agents for producing fine nanoemulsions and enhancing the oral bioavailability of rivaroxaban in SNEDDS.