• Journal of Pharmaceutical Investigation
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• 제41권4호
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• pp.239-247
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• 2011

Simvastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, which catalyzes the conversion of HMG-CoA to mevalonate, an early and rate-limiting step in the biosynthesis of cholesterol. Simvastatin has good permeability, but it also has low solubility (BCS class II), which reduces its bioavailability. To overcome this problem, a solid dispersion is formed using a spray-dryer with polymeric material carrier to potentially enhance the dissolution rate and extend drug absorption. As carriers for solid dispersion, Gelucire$^{(R)}$44/14 and Gelucire$^{(R)}$ 50/13 are semisolid excipients that greatly improve the bioavailability of poorly-soluble drugs. To avoid any toxic effects of an organic solvent, we used aqueous medium to melt Tween$^{(R)}$ 80 and distilled water. The structural behaviors of the raw materials and the solid dispersion were analyzed by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM). The DSC and PXRD data indicated that the crystalline structure of simvastatin was transformed to an amorphous structure through solid dispersion. Then, solid dispersion-based tablets containing 20 mg simvastatin were prepared with excipients. Dissolution tests were performed in distilled water and artificial intestinal fluid using the USP paddle II method. Compared with that of the commercial tablet (Zocor$^{(R)}$ 20 mg), the release of simvastatin from solid dispersion based-tablet was more efficient. Although the stability study is not complete, this solid dispersion system is expected to deliver poorly water-soluble drugs with enhanced bioavailability and less toxicity.

• 폴리머
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• 제35권4호
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• pp.277-283
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• 2011

고체분산체는 난용성 약물의 용출률 개선을 위한 방법으로 주로 사용된다. 난용성 약물인 프란루카스트를 플라스돈 S-630과 함께 분무건조하여 고체분산체를 제조하였다. pH에 따른 프란루카스트 용해도 실험을 실시하여 높은 pH에서 약물의 용해도가 높게 나왔다. 입도 분석으로 고체분산체 내의 약물의 크기가 나노 크기로 작아진 것을 확인하였다. 표면전위를 측정하여 고체분산체가 음전하를 가지고 있는 것을 확인하였다. 주사전자현미경으로 고체분산체의 표면이 구형임을 확인하였고, 시차주사열량계와 X-선 회절 분석법을 통해 고체분산체가 무정형임을 확인하였다. 고체분산체의 용출특성을 알아보기 위해 인공장액(pH 6.8)에서 용출거동을 확인하였고, 대조실험을 위해 시판제인 오논$^{(R)}$캡슐을 사용하였다. 이 결과로 분무건조를 통한 고체분산제의 제조를 통해 난용성 약물의 용출특성을 확인하였고, 경구용 약제학적 형태를 가질 수 있는 것을 확인하였다.

• Journal of Pharmaceutical Investigation
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• 제40권6호
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• pp.339-345
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• 2010

Fenofibrate has been used for many years to lower cholesterol levels and its pharmacokinetic profile is well understood. However, due to its low solubility in water, it has low bioavailability after oral administration. In order to improve the dissolution rate, fenofibrate was formulated into a self-microemulsifying drug delivery systems (SMEDDS). We used pseudo-ternary phase diagrams to evaluate the area of microemulsification, and an in vitro dissolution test was used to investigate the dissolution rate of fenofibrate. The optimized formulation for in vitro dissolution assessment consisted of Lauroglycol FCC (60%), Solutol HS 15 (27%), and Transcutol-P (13%). The mean droplet size of the oil phase in the microemulsion formed from the SMEDDS was about 130 nm. The dissolution rate of fenofibrate from SMEDDS was significantly higher than that of the reference tablet. Our studies suggested that the fenofibrate containing SMEDDS composition can effectively increase the solubility and oral bioavailability of poorly water-soluble drugs.

• Journal of Pharmaceutical Investigation
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• 제40권spc호
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• pp.83-95
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• 2010

Over the years, nanoparticle drug delivery systems have demonstrated versatile potentials in biological, medical and pharmaceutical applications. In the pharmaceutical industry nanotechnology research has mainly focused on providing controlled drug release, targeting their delivery to specific organs, and developing parenteral formulations for poorly water soluble drugs to improve their bioavailability. Achievement in polymer industry has generated numerous polymers applicable to designing nanoparticles. From viewpoints of product development, a nanocarrier material should meet requirements for biodegradability, biocompatibility, availability, and regulatory approval crieteria. Albumin is indeed a material that fulfills such requirements. Also, the commercialization of a first albumin-bound paclitaxel nanoparticle product (Abraxane$^{TM}$) has sparked renewed interests in the application of albumin in the development of nanoparticle formulations. This paper reviews the intrinsic properties of albumin, its suitability as a nanocarrier material, and albumin-based parenteral formulation approaches. Particularly discussed in detail are albumin-based particulate injectables such as Abraxane$^{TM}$. Information on key roles of albumin in the nab$^{TM}$ technology and representative manufacturing processes of albumin particulate products are provided. It is likely that albumin-based particulate technology would extend its applications in delivering drugs, polypeptides, proteins, vaccines, nucleic acids, and genes.

• Archives of Pharmacal Research
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• 제23권1호
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• pp.66-71
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• 2000

Peonjahwan, an oriental traditional medicine composed of crude herbal drugs and animal tissues is bitter and poorly water-soluble. To mask the bitterness of peonjahwan and enhance the release of bilirubin, one of the crude active ingredients of peonjahwan, peonja dry elixir (PDE), was prepared using a spray-dryer after extracting the crude materials in ethanol-water solution. coated peonja dry elixir (CPDE) was then prepared by coating the PDE with Eudragit acrylic resin. Panel assessed bitterness and release test of bilirubin from PDE and CPDE were carried out and compared with peonjahwan alone. PDE was found to have little effect upon the reduction of the bitterness of peonjahwan. However, the bitterness of CPDE was found to reduce to 1/4 of that of peonjahwan due to the encapsulation of crude active ingredients by the dextrin and Eudragit shell (P<0.05). The release rate of bilirubin from PDE and CPDE for 60 min increased about 3.5- and 2.5-fold, respectively, compared to peonjahwan at pH 1.2. It is concluded that CPDE, which masked the bitterness of peonjahwan and enhanced the release of bilirubin, is a preferable delivery system for peonjahwan.

• KSBB Journal
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• 제26권4호
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• pp.283-292
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• 2011

Solid dispersion is one of well-established pharmaceutical techniques to improve the dissolution and consequent bioavailability of poorly water soluble drugs. It is defined as a dispersion of drug in an inert carrier matrix. Solid dispersions can be classified into three generations according to the carrier used in the system. First and second generations consist of crystalline and amorphous substances, respectively. Third generation carriers are surfactant, mixture of polymer and surfactants, and mixture of polymers. Solid dispersions can be generallyprepared by melting method and solvent method. While melting method requires high temperature to melt carrier and dissolve drug, solvent method utilizes solvent to dissolve the components. The improvement in dissolution through solid dispersions is attributed to reduction in drug particle size, improvement in wettability, and/or formation of amorphous state. The primary characteristics of solid dispersions, the presenceof drug in amorphous state, could be determined by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and fourier-transformed infrared spectroscopy (FTIR). In spite of the significant improvement in dissolution by solid dispersion technique, some drawbacks have limited the commercial application of solid dispersions. Thus, further studies should be conducted in a direction to improve the congeniality to commercialization.

• 대한화학회지
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• 제50권6호
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• pp.464-470
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• 2006

약물인 덱사메타손은 효과적인 염증치료제이다. 그러나 난용성 약물로써 수용액에서 주사제로 가용화가 어렵다. 따라서 º ¿±¸에서는 ¸Þ¸손을 수용액상에서 주사제로 가용화하기 §Ø¼­ 지질로 만들어진 나노입자에 ¸Þ¸손을 봉입하여 체내투여 시 약물을 서서히 방출할 수 ´ 약물전달체를 제조하고자 ¿´´. 지질나노입자는 인지질, 콜레스테롤 ±×¸?簾? 양이온성 지질을 사용하여 자발 유화 ¿매확산법에 의해 제조하였다. ³ª노입자는 다양한 지질 종류와 지질의 함량에 따라서 봉입효율, 기 그리고 표면전하와 °°º ¹°리적 특성을 평가하였다. 기는 80~120 nm ¿´¸¸, 봉입효율은 80% 이상의 높은 효율을 보였다. 질의 지방쇄의 길이가 ±æ¼· 봉입효율은 증가하였고, 콜레스테롤의 량과 봉입효율은 반비례하였다. 나노지질입자는 양이온성 지질 없이는 형성되지 않았으며 ¾온성 지질의 ·?閻?¡ 따라서 봉입효율은 °¡하였다. 덱사메타손이 봉입된 지질나노입자는 난용성 약물을 주사제로 가용화 수 ´ 새로운 약물전달체로써의 가능성을 기대하는 바이다.

• Journal of Pharmaceutical Investigation
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• 제33권1호
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• pp.7-14
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• 2003

The PVP-based solid dispersion systems (SDs) containing lovastatin (LOS) and solubilizers (sodium lauryl sulfate, tween 80 and oleic acid) were prepared to enhance dissolution rate of practically water insoluble LOS using solvent evaporation method. Two different organic cosolvents either acetone/ethanol or acetonitrile/ethanol were used for the preparation of SDs. The LOS contents were highly decreased when acetone/ethanol cosolvents were used. The decrease of LOS contents was not caused by acetonitrile or acetone, based on HPLC data. The surface morphology as investigated by scanning electron microscope (SEM) and angle of repose as an index of flowability of SDs were highly dependent on the type and amount of solubilizers used. Based on differential scanning calorimetry (DSC) and X-ray powder diffraction data, the SDs made crystalline LOS into amorphous structure or partially eutectic mixtures. The simultaneous use of the solubilizers in SDs was also useful to increase dissolution rate of LOS in gastric or intestinal fluid. The SDs containing solubilizers reached 76% and 60% in gastric and intestinal fluid, respectively but the commercial tablet gave only less than 4%. These solubilizers in SDs could be also applicable for enhancing dissolution and bioavailability of poorly water-soluble drugs.

• Journal of Pharmaceutical Investigation
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• 제36권6호
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• pp.355-361
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• 2006

Intraarticular corticosteroid injections for therapy of rheumatic arthritis are administered with the aim of optimal local anti-inflammatory effect at the injection site. Since the side effects of corticosteroidal drug, dexamethasone(DEX), administered at hish dose limited the therapeutic efficacy, there was a need to design a new drug delivery system for controlled release of dexamethasone. As a prodrug for continuous therapeutic efficacy, dexamethasone-21-palmitate(DEX-PAL) was prepared via esterification of palmitoyl chloride and dexamethasone. DEX-PAL was identified by NMR and MASS analysis. DEX-PAL or DEX was entrapped in lipid nanosphere which could be prepared by using a self emulsification-solvent evaporation method. Physicochemical characteristics such as mean particle diameter, zeta potential and drug loading efficiency of the lipid nanospheres were investigated with variation of either the kind of lipid or the lipid composition. The lipid nanospheres had a mean diameter $83{\sim}95$ nm and DEX-PAL loading efficiency of up to 95%. The drug loading efficiency increased with the increase of aliphatic chain length attached to the phospholipid. The incorporation of cationic lipid was very efficient for both reducing particle size of lipid nanospheres and enhancing drug loading efficiency. The lipid nanospheres containing DEX-PAL may be a promising novel drug carrier for the controlled release of the poorly water-soluble drugs.

• Journal of Pharmaceutical Investigation
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• 제41권3호
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• pp.125-142
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• 2011

Solid dispersion, defined as the dispersion of one or more active ingredient in a carrier or matrix at solid state, is an efficient strategy for improving dissolution of poorly water-soluble drugs for enhancement of their bioavailability. Compared to other conventional formulations such as tablets or capsules, solid dispersion which can be prepared by various methods has many advantages. However, despite numerous studies which have been carried out, limitations for commercializing these products remain to be solved. For example, during the manufacturing process or storage, amorphous form of solid dispersion can be converted into crystalline form. That is, the dissolution rate of solid dispersion would continuously decrease during storage, resulting in a product of no value. To resolve these problems, studies have been conducted on the effects of excipients. In fact, modification of the solid dispersions to overcome these disadvantages has progressed from the first generation to the recent third generation products. In this review, an overview on solid dispersions in general will be given with emphasis on the various manufacturing processes which include the use of polymers and on the stabilization strategies which include methods to prevent crystallization.