Solubility enhancement studies of hydrochlorothiazide by preparing soliddispersions using losartan potassium and urea by different methods
Solubility enhancement studies of hydrochlorothiazide by preparing soliddispersions using losartan potassium and urea by different methods
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不同方法氯沙坦钾与尿素制备固体分散体增溶氢氯噻嗪的研究
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发表时间：
2011
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通讯作者：
M. Umekar
中科院分区：
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作者：
R. Trivedi;Pravin S. Admane;Jayashree B. Taks;J. Mahore;M. Umekar
水溶性差的药物是这类药物良好生物利用度的主要挑战之一。氢氯噻嗪（HCT）是BCS II类药物之一，水溶性较差，但其溶解度较低，因此，采用作为盐、络合、固体分散等方法来提高药物的溶解度。因此，为了通过固体分散技术增加其水溶性，使用了许多惰性载体。HCT与氯沙坦钾联合用于管理高血压。本研究采用氯沙坦钾为载体制备HCT固体分散体（SDL）以及氯沙坦钾与惰性载体尿素联合制备HCT固体分散体（SDLU）。采用物理混合法、糊剂法、溶剂挥发法和熔融法制备固体分散体。其中溶剂挥发法制备的SDL和SDLU具有最大的溶解度。FTIR研究证实药物和辅料之间不存在任何物理相互作用。XRD研究显示药物的结晶形式转化为无定形形式，因此溶解度增加。采用直接压片法制备了SDTL和SDTLU片，并与市售的HCT和氯沙坦钾片进行了释放度比较。药物释放研究表明，在90分钟时，发现SDTLU释放的HCT最大，即88.24 ± 0.04，与SDTL（74.45 ± 0.17）和市售片剂（62.46 ± 0.20）相比。因此，所进行的研究显示出将氯沙坦钾和尿素一起使用以将HCT的水溶解度提高至标记的良好范围，特别是当HCT与氯沙坦钾组合使用时。
Drugs having poor aqueous solubility present one of the major challenges for good bioavailability of such drugs. Many approaches have been used for solubility enhancement such as salt formation, complexation, solid dispersion etc. Hydrochlorothiazide (HCT) is one of the BCS class II drug having poor water solubility. Thus to increase its water solubility by solid dispersion technique many inert carriers are employed. HCT is used in combination of losartan potassium for management of hypertension. In present investigation we have used novel method by employing losartan potassium as a carrier for solid dispersion of HCT (SDL) as well as both losartan potassium and inert carrier urea in combination for solid dispersion of HCT (SDLU). Both the solid dispersions were prepared by physical mixture, paste method, solvent evaporation method and fusion method. Out of this SDL and SDLU prepared by solvent evaporation method exhibited maximum solubility. The FTIR study confirmed absence of any physical interaction between drugs and excipients. The XRD studies show the conversion of crystalline form of drug into amorphous form and hence, increase in the solubility. Tablets of SDTL and SDTLU were prepared by employing direct compression method and their release profiles were compared with marketed tablet containing HCT and losartan potassium. Drug release studies showed that at 90 mins release of HCT by SDTLU was found to be maximum i.e. 88.24±0.04 as compared to SDTL (74.45±0.17) and marketed tablet (62.46±0.20). Thus the studies carried out exhibited good scope of using losartan potassium and urea together for enhancing the aqueous solubility of HCT up to the mark especially when HCT is to be used in combination with Losartan potassium.