Formulation optimization of orally disintegrating tablets containing solid dispersion of felodipine and hydroxypropyl methylcellulose using face-centered central composite design

Nguyen-Thach Tung,Man-Van Hung,Xuan-Minh Vo,Thanh-Hai Nguyen,Thi-Minh-Hue Pham 한국약제학회 2014 Journal of Pharmaceutical Investigation Vol.44 No.2

A novel dosage form integrating solid dispersion(SD) in orally disintegrating tablets (ODTs) wasdeveloped and optimized by the face-centered centralcomposite design to improve poorly soluble property andslow onset action time of felodipine (Fel). SD of Fel andhydroxypropyl methylcellulose E6 was prepared by solventevaporation method. Differential scanning calorimetry andfourier transforms infrared spectroscopy indicated that Feltransformed from crystalline to amorphous state by theformation of hydrogen bond between –N–H in Fel and O–Rin HPMC. The accelerated stability test in 45 C, 75 % RHdemonstrated that the optimized SD was stable in terms ofthe dissolution rate of Fel and thermodynamic property. The ODTs containing SD (Fel:HPMC E6 = 1:3) wereprepared by direct compression technique. The face-centeredcentral composite design with the ODT-SD wasemployed to investigate the effect of mannitol (X1),crospovidone XL (X2) on the ODT-SD disintegration time(Y1), % Fel released after 5 min (Y2) and the ODT-SDfriability (Y3). ANOVA test showed that X2 and X2 * X2had a significant effect on the ODT-SD disintegration time(p\0.05). Meanwhile, the dissolution rate of Fel after5 min did not remarkably depend on any independentvariables (p[0.05). The ODT-SD friability was substantiallyproportional to the amount of mannitol (X1)(p\0.05). The optimized ODT-SD disintegration time, %Fel released after 5 min, and friability were 27.67 s, 88.35and 0.48 %, respectively.

Formulation and in vivo imaging evaluation of colonic targeting tablets prepared by a simple dry powder coating technique

Tung Nguyen-Thach,Nguyen Canh-Hung,Nguyen Van-Duong,Nguyen Thi-Hong-Thuy,Nguyen Van-Lam,Tran Cao-Son,Pham Thi-Minh-Hue 한국약제학회 2020 Journal of Pharmaceutical Investigation Vol.50 No.4

Purpose The study aimed firstly to determine the release behavior of the model drug (berberine chloride) from the dry coated tablets. The second objective of this study was to evaluate the exact location of the dry coated tablets in in vivo. Methods The colon targeting tablets were developed by dry powder coating technique on pan coater. The drug release behavior was determined in the three continuous mediums: pH 1.2; 7.4 and 6.8 plus pectinase. The location of the dry coated tablets in the gastrointestinal tract of human volunteers was observed through the X-ray imaging of the dry coated tablets containing the optimized radiocontrast agents. Results The release kinetics of berberine chloride from the dry coated tablets was mainly controlled by erosion and enzyme sensitive mechanism. The optimum dry coated tablets having the coating powders of pectin 102:HPMC K4 M (2:1) with the coating level of 200%, and the tablet core with BaSO4 10% and iobitridol 30% as radiocontrast agents were observed in the caecum and ascending colon of human volunteers after 5–6 h of oral administration. Conclusion The successful development of these dosage forms is believed to have a high potential in precisely monitoring the release of highly potent drugs such as anti-inflammatory drugs in bowel diseases.

Topical delivery of dexamethasone acetate from hydrogel containing nanostructured liquid carriers and the drug

Nguyen-Thach Tung,Vu-Thu Huyen,지상철 대한약학회 2015 Archives of Pharmacal Research Vol.38 No.11

The potential of hydrogel containing nanostructuredlipid carriers (NLC) to enhance the skin permeationrate and skin deposition of dexamethasone acetate(DEA) was investigated. The particle size of obtainedNLCs was around 224.4 nm. NLCs had core–shell structureand DEA existed in amorphous state in NLCs. Thepermeation rate of DEA through excised mouse skins fromhydrogel containing DEA–NLC (DEA–NLC-hydrogel)was 7.3 times higher than DEA-ointment. The skin depositionof DEA from DEA–NLC-hydrogel increased 3.8folds compared to that from solution of DEA in hydrogel(DEA-hydrogel).

A two-step design of experiments approach to investigate the simultaneous effects of ion-pairing and chemical enhancers to improve the permeability of lornoxicam in a topical hydrogel patch

Nguyen Huu-Manh,Duong The-Khang,Nguyen Van-Khuyen,Nguyen Thi-Khanh-Ly,Dong Thi-Hoang-Yen,Nguyen Canh-Hung,Tung Nguyen-Thach 한국약제학회 2024 Journal of Pharmaceutical Investigation Vol.54 No.2

Purpose A two-step experimental design was used to develop a lornoxicam (LOR)-loaded topical hydrogel patch. We specifically focused on the simultaneous effect of the ion pair formation agent (triethanolamine [TEA]) and the chemical enhancer (cremophor RH40 [RH40]) on flux and conducted physicochemical studies and skin physiology assessments to obtain further information. Methods Drug-in-adhesive patches were fabricated using a micrometer-adjustable film applicator. The applied Design of Experiments (DoE) approach consisted of the Fractional Factorial Resolution V + design and the Central Composite Face design established by the MODDE® 12.0 software. Molecular-level drug-excipient interactions were investigated using infrared (IR) and proton nuclear magnetic resonance (1H NMR) spectroscopy. The effects on skin physiological function was assessed using DermaLab Combo. Results DoE results revealed that TEA enhanced flux by 3.14-fold, whereas RH40 reduced it by 4.62-fold. The addition of RH40 resulted in the disappearance of the proton peak within the region of 12–13 ppm, suggesting competition for hydrogen bonding with LOR between TEA and RH40. The optimized formulation (4% TEA, 0% RH40, and 0.2% Al(OH)3) increased skin hydration by 6.20-fold. Opposing effects of TEA and RH40 on skin elasticity were observed. Conclusion Expected flux and adhesion strength for the optimized formulation were 7.18 μg·cm–2·h–1 and 11.79 mJ, respectively. Our understanding of the conflicting effects of TEA and RH40 has been advanced. The integrated use of the two-step DoE, physicochemical studies, and skin physiology assessments was proven to be effective in elucidating the simultaneous effects of different permeation-modifying strategies on patches, thus having substantial value for the successful execution of future research endeavors.

Preparation and in vivo evaluation of immediate-release pellet containing celecoxib solid dispersion

Park, Chun-Woong,Tung, Nguyen-Thach,Son, Dao-Danh,Kim, Ju-Young,Rhee, Yun-Seok,Kang, Seung-Yeop,Park, Shin-Ae,Hwang, Kyu-Mok,Oh, Tack-Oon,Ha, Jung-Myung,Chi, Sang-Cheol,Park, Eun-Seok 한국약제학회 2012 Journal of Pharmaceutical Investigation Vol.42 No.3

The aim of this study was to make use of small size of immediate-release (IR) pellet and amorphous state of solid dispersion to increase solubility of celecoxib (CLX), a drug in BCS class II. Primary, binary and ternary solid dispersions were developed to choose the final components for solid dispersion. A ternary novel solid dispersion was prepared by incorporation of one aqueous soluble polymer (povidone k17; PVP 17PF), Methacrylate copolymer-based gastric soluble polymer ($Eudragit^{(R)}$ EPO) and one pH modulator (MgO). This combination was effective to increase solubility in pH 1.2 up to 25-30 %. The mechanism of solubility enhancement was proven by DSC, PRXD, and FT-IR. Accordingly, hydrogen bonding or electrostatic interaction of CLX with PVP/$Eudragit^{(R)}$ EPO was the main cause to form the amorphous state of CLX within polymer cluster which increasing solubility of drug. Besides, MgO played an important role to change microenviroment for solid dispersion. Pellets containing this solid dispersion were prepared by extrusion and spheronization technique. Effect of four kinds of additive (calcium hydrogen phosphate dihydrate,$NaHCO_3$, crospovidone, and sodium dodecyl sulfate) on dissolution of CLX from IR pellet was also determined. Because of highest dissolution rate, formulation using sodium dodecyl sulfate was used for pharmacokinetics study. Solid dispersion-IR pellet formulation presented bioequivalence and lower variability in comparison with reference product.

Preparation and in vivo evaluation of immediate-release pellet containing celecoxib solid dispersion

Chun-Woong Park,Nguyen-Thach Tung,Dao-Danh Son,김주영,이윤석,Seung-Yeop Kang,Shin-Ae Park,황규목,오택운,하정명,Sang-Cheol Chi,박은석 한국약제학회 2012 Journal of Pharmaceutical Investigation Vol.42 No.3

The aim of this study was to make use of small size of immediate-release (IR) pellet and amorphous state of solid dispersion to increase solubility of celecoxib (CLX), a drug in BCS class II. Primary, binary and ternary solid dispersions were developed to choose the final components for solid dispersion. A ternary novel solid dispersion was prepared by incorporation of one aqueous soluble polymer (povidone k17; PVP 17PF), Methacrylate copolymer-based gastric soluble polymer (Eudragit EPO) and one pH modulator (MgO). This combination was effective to increase solubility in pH 1.2 up to 25–30 %. The mechanismof solubility enhancement was proven by DSC, PRXD, and FT-IR. Accordingly, hydrogen bonding or electrostatic interaction of CLXwithPVP/EudragitEPOwas themain cause to formthe amorphous state of CLX within polymer cluster which increasing solubility of drug. Besides, MgO played an important role to change microenviroment for solid dispersion. Pellets containing this solid dispersion were prepared by extrusion and spheronization technique. Effect of four kinds of additive (calciumhydrogen phosphate dihydrate,NaHCO3,crospovidone, and sodium dodecyl sulfate) on dissolution of CLX from IR pellet was also determined. Because of highest dissolution rate, formulation using sodium dodecyl sulfate was used for pharmacokinetics study. Solid dispersion-IR pellet formulation presented bioequivalence and lower variability in comparison with reference product.