Enhanced Solubility Through Particle Size Control, Modification of Crystal Behavior, and Crystalline Form Changes in Solid Dispersion of Nifedipine

정주영,신광일,이민선,송명관,권순조 한국생물공학회 2022 Biotechnology and Bioprocess Engineering Vol.27 No.1

The purpose of this study was to investigate the selectivity of polymers and the suitability of spray drying to enhance nifedipine solubility. Nifedipine alone or in combination with polymers was dissolved in a mixed solvent of methylene chloride and ethanol. The hydrophilic polymers used were PVP K-30, HPMC, HPMCP, Eudragit, and HPMCAS. Each solid dispersion was prepared using a laboratory spray dryer. The spray-dried solid dispersants were characterized by SEM, DSC, and XRPD analysis, and dissolution tests compared the dissolution rates of nifedipine solid dispersants and nifedipine. The results showed that all spray-dried solid dispersions were in an amorphous form. Dissolution tests were performed at pH 1.2 (artificial gastric juice) and pH 6.8 (artificial intestinal juice) to evaluate solid dispersion solubility. The solid dispersion containing HPMC showed a notably enhanced dissolution rate under both pH conditions. Interestingly, HPMCP and HPMCAS showed almost no enhancement of dissolution behavior at pH 1.2, but a significant increase (10 times or higher) over that of the pure polymer at pH 6.8. Solubility enhancement of poorly soluble drugs differs markedly among the polymers used for spray drying. From the results, HPMCP and HPMCAS are suitable as carriers for drugs with poor solubility that require acid resistance.

Comparative study on solid self-nanoemulsifying drug delivery and solid dispersion system for enhanced solubility and bioavailability of ezetimibe

( Rehmana Rashid ),( Dong Wuk Kim ),( Abid Mehmood Yousaf ),( Omer Mustapha ),( Fakhar Ud Din ),( Jong Hyuck Park ),( Chul Soon Yong ),( Yu Kyoung Oh ),( Yu Seok Youn ),( Jong Oh Kim ),( Han Gon Choi 영남대학교 약품개발연구소 2016 영남대학교 약품개발연구소 연구업적집 Vol.26 No.-

Background: The objective of this study was to compare the physicochemical characteristics, solubility, dissolution, and oral bioavailability of an ezetimibe-Ioaded solid self-nanoemulsifying drug delivery system (SNEDDS), surface modified solid dispersion (SMSD), and solvent evaporated solid dispersion (SESD) to identify the best drug delivery system with the highest oral bioavailability. Methods: For the liquid SNEDDS formulation, Capryol 90, Cremophor EL, and Tween 80 were selected as the oil, surfactant, and cosurfactant, respectively. The nanoemulsion-forming region was sketched using a pscudotemary phase diagram on the basis of reduced emulsion size. The optimized liquid SNEDDS was converted to solid SNEDDS by spray drying with silicon dioxide. Furthermore, SMSDs were prepared using the spray drying technique with various amounts of hydroxypropylcellulose and Tween 80, optimized on the basis of their drug solubility. The SESD formulation was prepared with the same composition of optimized SMSD. The aqueous solubility, dissolution, physicochemical properties, and pharmacokinetics of all of the formulations were investigated and compared with the drug powder. Results: The drug existed in the crystalline form in SMSD, but was changed into an amor-phous form in SNEDDS and SESD, giving particle sizes of approximately 24, 6, and 11 urn, respectively. All of these formulations significantly improved the aqueous solubility and dis-solution in the order of solid SNEDDS "``: SESD > SMSD, and showed a total higher plasma concentration than did the drug powder. Moreover, SESD gave a higher area under the drug concentration time curve from zero to infinity than did SNEDDS and SMSD, even if they were not significantly different, suggesting more improved oral bioavailability. Conclusion: Among the various formulations tested in this study, the SESD system would be strongly recommended as a drug delivery system for the oral administration of ezetimibe with poor water solubility.

용해도가 개선된 티카그렐러 고체분산체 함유 정제의 개발

최형주(Hyung Ju Choi),김경수(Kyeong Soo Kim) 대한약학회 2020 약학회지 Vol.64 No.1

The objective of this study was to develop a novel ticagrelor (TC) solid dispersion-loaded tablet with enhanced solubility. Numerous polymers and surfactant were screened, and then Kollidon VA64 and Poloxamer 407 were selected as a soluble polymer and a surfactant for preparing TC solid dispersions. Various solid dispersions were prepared by spraydrying process, and the physicochemical properties, solubility and dissolution profile were investigated. The TC solid dispersion consisted of TC, Kollidon VA64, Poloxamer 407 and colloidal silica at a weight ratio of 1/1/4/1, provided an amorphous drug and spherical particle shape. Moreover, it exhibited excellent solubility and dissolution rate compared to the TC. The TC solid dispersion-loaded tablet were prepared and their dissolution were evaluated compared to commercial TC tablet. The required time for complete release of the TC solid dispersion and the TC solid dispersion-loaded tablet were within 60 min and 8 hrs in various dissolution media. However commercial TC tablets showed low dissolution rate less than 10% in pH 1.2, 4.0 and 6.8 buffer up to 8 hrs. Thus, we successfully prepared the TC solid dispersion-loaded tablet for enhancing solubility of TC and this novel TC solid dispersion-loaded tablet could be a potential alternative for commercial TC tablet.

Design, optimization, and evaluation of ezetimibe solid supersaturatable self-nanoemulsifying drug delivery for enhanced solubility and dissolution

Rajendra Narayan Dash,Habibuddin Mohammed,Touseef Humaira 한국약제학회 2016 Journal of Pharmaceutical Investigation Vol.46 No.2

This study was intended to develop a solid supersaturatable self-nanoemulsifying drug-delivery system (solid S-SNEDDS) to improve the solubility and dissolution of a poorly water-soluble drug ezetimibe. Selfnanoemulsifying drug delivery system (SNEDDS) preconcentrate was systematically optimized by a central composite design (a = 1.682). The optimized SNEDDS preconcentrate consisted of Captex 355 (30 % w/w), Cremophor RH40 (40 % w/w) and Imwitor 988 (30 % w/w). Saturation solubility of ezetimibe in the optimized SNEDDS preconcentrate was found to be 90.62 mg/ml. HPMC-E5 (5 % w/w) and ezetimibe (90 % saturation solubility level) were added to the SNEDDS preconcentrate to form a supersaturatable SNEDDS (liquid S-SNEDDS). Dilution of liquid S-SNEDDS resulted in a nanoemulsion having a mean droplet size of 27.3 nm. TEM studies of diluted liquid S-SNEDDS confirmed uniform shape and size of the droplets. The liquid formulation was adsorbed onto microcrystalline cellulose and talc to form a solid S-SNEDDS. In vitro supersaturation test of solid S-SNEDDS showed a higher ezetimibe concentration (that retarded precipitation of ezetimibe at least up to 60 min) in comparison to the solid-SNEDDS (without HPMC-E5). PXRD studies of the precipitates collected from the in vitro supersaturation test, revealed the presence of amorphous ezetimibe. DSC and SEM results indicated that the presence of ezetimibe in an amorphous and molecular dispersed state within the solid S-SNEDDS. In vitro release (in 15 min) of ezetimibe from solid S-SNEDDS improved by 1.17, 1.69, and 13.21-fold as compared with solid- SNEDDS, commercial product, and the free drug (powder), respectively.

수경재배한 토마토의 품종별 품질특성 비교 및 품질특성간 상관관계

이스람모하메드조히를(Islam Mohammad Zahirul),유태종(Tae-Jong Yoo),정현진(Hyun Jin Jung),최인이(In-Lee Choi),전신재(Shin Jea Jeon),원재희(Jae Hee Won),이윤석(Youn Suk Lee),김영식(Young Shik Kim),김일섭(Il Seop Kim),강호민(Ho-Min Kang) (사)한국생물환경조절학회 2010 생물환경조절학회지 Vol.19 No.2

본 연구는 국내에서 주로 생산되고 있는 대과종 토마토 품종의 품질을 비교 조사하여, 토마토의 원활한 유통 및 수출을 위한 수확후 관리 분야의 연구의 기초 자료를 얻고자 수행되었다. 과피색은 품종별 일정한 경향 없이 a*/b 값은 2.8에서 4.8범위 안에 있었다. 호흡률과 에틸렌 발생률도 품종간 큰 차이를 보이지는 않았다. 내적 품질 중 경도는 ‘Picasso’, ‘Tymaxx’, ‘Madison’에서 가장 높았다. 당도의 경우 대체로 6°Brix 수준을 나타내었는데 ‘Hoyong’과 ‘Dotearang Dia’가 높았다. 비타민 C 함량은 ‘Super Sunroad’와 ‘Dotearang Dia’가 가장 높았다. 산도는 품종별 큰 차이 없이 ‘Hoyong’이 가장 높았으며, 이 때문에 당산비는 당도와 유사한 양상으로 유럽계 중 당도가 낮았던 ‘Amaral’, ‘Picasso’, ‘Tymaxx’에서 낮았다. 이상의 결과로 보면 수출 토마토에서 중요한 품질 요인인 경도는 유럽계가 당도와 비타민 C 함량은 동양계가 높았다. 품질 요인간 상관관계는 a*/b* 값으로 표시한 과피색이 여러 품질 요인과 높은 상관관계를 나타내었는데, 특히 당도와 가장 높은 상관계수(r = 0.801)를 나타내었다. 또한 수출현장에서 중요하게 다루는 경도와 당도는 부의 상관관계(r = ?0.601)를 나타내었다. This study was conducted to compare the quality characters of 15 different tomato cultivars (‘Dotearang Dia’, ‘Super Dotearang’, ‘Super sunroad’, ‘Hoyong’, ‘Mirokku’, ‘Baccuhs’, ‘Mascara’, ‘Poseidon’, ‘Radido’, ‘Madison’, ‘Rapsodie’, ‘Solomon’, ‘Amaral’, ‘Picasso’, ‘Tymaxx’) and find out the correlation among the quality characters in order to get basic informations for exporting tomato. The a*/b* value of fruit surface showed from 2.8 to 4.8, but there was no significant difference in fruit surface color value, such as a*, b* and a*/b* among the cultivars. The respiration and ethylene production rate also were not shown any significantly difference among cultivars. The firmness of fruit was higher in ‘Picasso’, ‘Tymaxx’ and ‘Madison’ cultivars. The contents of soluble solids was higher in ‘Hoyong’ and ‘Dotearang Dia’ cultivars. The vitamin C content was higher in ‘Super Sunroad’ and ‘Dotearang Dia’ cultivars. The titratable acidity was higher in ‘Hoyong’ cultivars. The sugar/acid ratio that depended on soluble contents was lower in ‘Amaral’, ‘Picasso’, ‘Tymaxx’ cultivars that showed lower soluble contents. Conclusionally, The firmness that was one of the most important quality character in exporting tomato was higher in European cultivars, but soluble solide and vitamin C content were higher in Japanese cultivars. The significant correlation coefficient values were determined (more than p = 0.05) between a*/b* and other quality characters. The results suggested that surface color was the most suitable character represented tomato qualities. The high coefficient value (r = 0801) between a*/b* and the contents of soluble solids. The firmness and the contents of soluble solids that is the most important factor for exporting showed significant negative correlation (r = ?0.611).

‘Shine Muscat’ 포도의 적정 착과량 및 수확기준 설정

김준혁,정명희,박요셉,이별하나,박희승 한국원예학회 2019 원예과학기술지 Vol.37 No.2

The aim of this study is to ascertain suitable harvesting time and yields for the development of colorchart for the establishment of harvesting standard based on the skin color of ‘Shine Muscat’ grapes. The experiment was conducted at an orchard in Cheonan, Gyeonggi-do, Korea and clusters per vinewere set to harvest 1,800 kg, 2,100 kg and 2,400 kg per 10 a. Even though the yield was increasedup to 2,400 kg per 10 a, there was no difference in the size of the fruit. However, with regard to fruitquality, grapes controlled to 2,400 kg per 10 a had lower soluble solids content, poorer coloring,higher acidity and hardness compared to other grapes controlled to 1,800 kg and 2,100 kg. Also, thechlorophyll content of grapes controlled to 2,400 kg per 10 a was higher compared to other grapes. Accordingly, for ‘Shine Muscat’ grape cultivation, it is considered that controlling the yield to lessthan 2,100 kg per 10a is effective in terms of fruit quality. Soluble solids content in grapes controlledto 1,800 kg and 2,100 kg per 10 a, exhibited a continuous increase with progress in ripening. Theacidity and soluble solid-acid ratio remained unchanged for about 110 days after full bloom. Also,the color stage reached the peak at 120 days after full bloom. Therefore, it is considered thatcontrolling the yield of ‘Shine Muscat’ grapes to within 2,100 kg per 10 a and harvesting 120 daysafter full are effective in meeting both productivity and fruit quality. To develop a color chart for thematured determination of ‘Shine Muscat’ grapes, the growing period was divided into 5 stages andbased on these stages; fruit quality and pigment content were compared. A color chart was made bydetermining the appropriate range of soluble solids content and acidity. 본 연구에서는 국내에서 재배되고 있는 ‘Shine Muscat’ 포도의 적정 착과량과 수확기를 구명하고, 과피색을 기준으로 한 숙기 판정용 칼라 차트를 개발하고자 하였다. 경기도 천안 소재 농가 포장에서 실험을 수행하였으며, 생산량은 10a당 1,800,2,100, 2,400kg으로 조절하였다. 10a당 2,400kg까지는 생산량이 증가해도 과실 크기에 차이가 없었으나, 과실 품질은 10a당188 Horticultural Science and Technology‘Shine Muscat’ 포도의 적정 착과량 및 수확기준 설정2,400kg 생산구가 다른 생산구에 비해 가용성 고형물 함량이 낮고 산 함량과 경도가 높으며 착색이 불량한 것으로 조사되었다. 엽록소 함량 또한 10a당 2,400kg 생산구가 다른 생산구에 비해 높게 조사되어, 고품질 과실 생산을 위해서는 ‘Shine Muscat’포도 재배 시 생산량은 10a당 2,100kg 이내로 조절하여야 할 것으로 생각되었다. 1,800kg 및 2,100kg 생산구의 시기별 과실 품질에 있어서 가용성 고형물 함량은 성숙이 진행될수록 계속해서 증가하였으며, 산 함량 및 당산비 모두 성숙이 진행될수록 계속 증가하다가 만개 후 110일 이후부터는 변화 없이 일정하게 유지되었다. 반면에 착색은 만개 후 120일에 최고치에 도달하였다. 따라서 ‘Shine Muscat’ 포도 재배 시 생산량을 10a당 2,100kg 이내로 조절하여, 만개 후 120일 이후에 수확하는 것이 생산성과 과실 품질을 동시에 충족시키는 데 효과적일 것으로 생각된다. ‘Shine Muscat’ 포도의 숙기 판정용 칼라 차트를 개발하기위해, 생육기를 5 단계로 구분하여, 이러한 단계들을 기준으로 과실의 품질과 색소 함량을 비교하였으며, 가용성 고형물 함량과 산 함량의 적정 범위를 구하여 칼라 차트를 작성하였다.

Physicochemical characterization and in vivo evaluation of flurbiprofen-loaded solid dispersion without crystalline change

Oh, Dong Hoon,Park, Young-Joon,Kang, Jun Heok,Yong, Chul Soon,Choi, Han-Gon Informa Healthcare 2011 Drug delivery Vol.18 No.1

<P>To develop a novel flurbiprofen-loaded solid dispersion without crystalline change, various flurbiprofen-loaded solid dispersions were prepared with water, sodium carboxylmethyl cellulose (Na-CMC), and Tween 80. The effect of Na-CMC and Tween 80 on aqueous solubility of flurbiprofen was investigated. The physicochemical properties of solid dispersions were investigated using SEM, DSC, and X-ray diffraction. The dissolution and bioavailability in rats were evaluated compared to commercial product. Unlike conventional solid dispersion systems, the flurbiprofen-loaded solid dispersion gave a relatively rough surface and changed no crystalline form of drug. These solid dispersions were formed by attaching hydrophilic carriers to the surface of drug without crystal change, resulting in changing the hydrophobic drug to hydrophilic form. Furthermore, the flurbiprofen-loaded solid dispersion at the weight ratio of flurbiprofen/Na-CMC/Tween 80 of 6/2.5/0.5 improved ∼ 60-fold drug solubility. It gave higher AUC, <I>T</I><SUB>max</SUB>, and <I>C</I><SUB>max</SUB> compared to commercial product. The solid dispersion improved almost 1.5-fold bioavailability of drug compared to commercial product in rats. Thus, the flurbiprofen-loaded solid dispersion would be useful to deliver poorly water-soluble flurbiprofen with enhanced bioavailability without crystalline change.</P>

Solid Dispersions of Dihydroartemisinin in Polyvinylpyrrolidone

Ansari, Muhammad Tayyab,Sunderland, Vivian Bruce 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.3

In the present study the physicochemical characteristics of dihydroartemisinin, polyvinylpyrrolidone and their solid dispersions were evaluated at various proportions of drug and polyvinylpyrrolidone. These properties were investigated with X-ray diffraction, fourier transform infrared spectrophotometry, differential scanning calorimetry, equilibrium solubility at twenty five and thirty seven degree centigrade. X-ray diffraction analysis detected that dihydroartemisinin became more amorphous as drug carrier ratio was enhanced in solid dispersions. Fourier transform infrared spectra suggested that there was a hydrogen bonding interaction between dihydroartemisinin and polyvinylpyrrolidone in all solid dispersions. These interactions reflected the changes in crystalline structures of dihydroartemisinin. The thermal behavior of dihydroartemisinin was unusual as it exhibited melting exotherm instead of endotherm. In solid dispersions containing varying contents of polyvinylpyrrolidone, enthalpy change and peak area were enhanced while melting onset temperature decreased with increase in polyvinylpyrrolidone proportion. This was attributed to a solid-state interaction. Equilibrium solubility of dihydroartemisinin increased sixty-fold due to induction of polyvinylpyrrolidone. When this solubility was compared among thirty-seven and twenty five degree centigrade in solid dispersions, it was up to seven times more at higher temperature. Physicochemical characteristics of solid dispersions containing drug carrier ratio of one: nine prepared in acetonitrile, ethanol, methanol and tetrahydrofuran showed differences which indicated that properties of medium i.e. dielectric constant, dipole moment and structure, influenced the amount of amorphousness and related properties of dihydroartemisinin.

Solid Dispersions of ihydroartemisinin in Polyvinylpyrrolidone

Muhammad Tayyab Ansari,Vivian Bruce Sunderland 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.3

In the present study the physicochemical characteristics of dihydroartemisinin, polyvinylpyrrolidone and their solid dispersions were evaluated at various proportions of drug and polyvinylpyrrolidone. These properties were investigated with X-ray diffraction, fourier transform infrared spectrophotometry, differential scanning calorimetry, equilibrium solubility at twenty five and thirty seven degree centigrade. X-ray diffraction analysis detected that dihydroartemisinin became more amorphous as drug carrier ratio was enhanced in solid dispersions. Fourier transform infrared spectra suggested that there was a hydrogen bonding interaction between dihydroartemisinin and polyvinylpyrrolidone in all solid dispersions. These interactions reflected the changes in crystalline structures of dihydroartemisinin. The thermal behavior of dihydroartemisinin was unusual as it exhibited melting exotherm instead of endotherm. In solid dispersions containing varying contents of polyvinylpyrrolidone, enthalpy change and peak area were enhanced while melting onset temperature decreased with increase in polyvinylpyrrolidone proportion. This was attributed to a solid-state interaction. Equilibrium solubility of dihydroartemisinin increased sixty-fold due to induction of polyvinylpyrrolidone. When this solubility was compared among thirty-seven and twenty five degree centigrade in solid dispersions, it was up to seven times more at higher temperature. Physicochemical characteristics of solid dispersions containing drug carrier ratio of one: nine prepared in acetonitrile, ethanol, methanol and tetrahydrofuran showed differences which indicated that properties of medium i.e. dielectric constant, dipole moment and structure, influenced the amount of amorphousness and related properties of dihydroartemisinin.

Solubility of Mixed Lanthanide Hydroxide and Oxide Solid Solutions

Moniruzzaman, Mohammad,Kobayashi, Taishi,Sasaki, Takayuki Korean Radioactive Waste Society 2021 방사성폐기물학회지 Vol.19 No.3

The solubilities of different multicomponent lanthanide oxide (Ln₂O₃) solid solutions including binary (Ln₁ and Ln₂ = La, Nd, Eu, or Tm), ternary (Ln₁, Ln₂, and Ln₃ = La, Nd, Eu, or Tm), and higher systems (Ln = La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu) were studied after aging for four weeks at 60℃. Our recent study revealed that the phase transformations in binary ((La, Nd) and (La, Eu)) and ternary (La, Nd, Eu) systems are responsible for the formation of (La, Nd)(OH)₃, (La, Eu)(OH)₃, and (La, Nd, Eu)(OH)₃ solid solutions, respectively. The variations in the mole fractions of La³⁺, Nd³⁺, and Eu³⁺ in the sample solutions of these hydroxide solid solutions indicated that a thermodynamic equilibrium might account for the apparent La, Nd, and Eu solubilities. Conversely, the binary and ternary systems containing Tm₂O₃ as the heavy lanthanide oxide retained the oxide-based solid solutions, and their solubility behaviors were dominated by their congruent dissolutions. In the higher multicomponent system, the X-ray diffraction patterns of the solid phases, before and after contact with the aqueous phase indicated the formation of a stable oxide solid solution and their solubility behavior was explained by its congruent dissolution.