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In order to solve the problems of erratic drug absorption and low bioavailability after oral administration for poorly-water soluble drugs due to low solubility, a series of novel pharmaceutical dosage forms as solid dispersion, liposome, microemulsion, vesicle, cyclodextrin inclusion complexes and drug nanocrystal have been developed in recent years. Among which drug nanocrystal attracts more attentions for its simpler preparation method, higher drug loading and easier manufacturing technology in the design of dosage forms suitable for different administration routes. In this paper, the nanocrystals of the poorly-water soluble drugs prepared based on bottom-up and top-down technologies were introduced. The characteristics and applications of the nanocrystal-based dosage forms as suspension, tablet and capsule were also introduced and carefully evaluated with the focus on their pharmacokinetics, pharmacodynamics and tissue targeted drug distribution after delivery by oral administration, intravenous injection and pulmonary inhalation. The advantages of drug nanocrystals in their therapeutics effects over the bulk drugs were discussed together with the inherent mechanism. Finally, the problems existing in basic research and scaled-up manufacture of drug nanocrystal as well as the possible ways of solution were listed out so as to make the nanocrystal-based preparations exert their maximum therapeutic effect after clinical application.
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italic>Tert-butanol is an organic solvent, widely used in the medical field and chemical industry. It could be characterized by high crystallization temperature and vapor pressure. It could be easily sublimed and removed during the freeze-drying process. This review mainly describes the use of tert-butanol in the lyophilized formulations of poorly soluble drugs, the lyophilization solvent of porous structure productions, and as an ice crystal growth guider. In addition, the application of tert-butanol in nano drugs and aerogels has also been reviewed, as well as the current research progress in its quality and safety.
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Biphasic dissolution test, consisting of immiscible aqueous and organic phase, is an in vitro dissolution method that simultaneously measures the dissolution and partition of drugs. Due to the advantages of simulating in vivo absorption and overcoming the influence of surfactants on dissolution, it has been widely used to evaluate the poorly soluble drugs in vitro dissolution. Based on the relevant research in this field in recent years, this review summarizes the history, dissolution device, theoretical model and application of the biphasic dissolution test. Finally, the prospects in the development of biphasic dissolution test are also outlined.
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OBJECTIVE: To prepare dissolving microneedles using Gantrez S-97 and PVPk30 as composite matrix materials to accelerate the delivery of poorly water soluble drugs and study the preparation, appearance, mechanical properties, intradermal solubility, drug efficacy and crystallization behavior of dissolving microneedles. METHODS: Using polydimethylsiloxane(PDMS) as the negative mode, microneedles were prepared by the reverse casting method. SEM was used to observe the morphological appearance of the microneedles. The mechanical properties of the microneedles were investigated by texture analyzer and histological sections. Delivery of lidocaine was characterized by intradermal dissolution and pharmacodynamics. Crystallization behavior of lidocaine was characterized by DSC. RESULTS: Lidocaine dissolving microneedles had good needle shape and possessed sufficient mechanical strength to penetrate into the skin. The microneedles could dissolve in the dermis within 3 min and retain anesthetic effect, and the drug existed in amorphous form in the microneedles. CONCLUSION: Cosolvent preparation of dissolving microneedles has potential for promoting the delivery of poorly water soluble drugs.
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To improve the dissolution and bioavailability of poorly water-soluble drugs have been being emphasis and difficulty in pharmaceutical research. Supercritical fluid precipitation(SFP) technology has an extensive prospect in new drug delivery systems of the poorly water-soluble drugs base on its advantages, such as green, friendliness to the environment and it is possible to achieve industrial-scale production. In this paper, related literatures were retrieved to summarize the application of SFP for preparation of poorly water-soluble drugs in recent years.
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To improve the in vitro dissolution and in vivo absorption as well as the bioavailability after oral administration by increasing the solubility with the formation of solid dispersion remains a great challenge for the oral dosage form design of poorly water-soluble drugs. Compared with the other pharmaceutical techniques in improving the solubility for poorly water-soluble drugs, priorities are usually given to solid dispersion for its manufacturing convenience. Following the characteristics introduction, we were focused this review on the novel carriers and advanced techniques used for preparing solid dispersions. Amphiphilic polymers used as novel solid dispersion carriers are Solutol HS 15, Soluplus and poly [MPC-co-BMA]. Inorganic materials like magnesium aluminum metasilicat, mesoporous silica microparticle and mesoporous magnesium carbonate are introduced together with the advanced solid dispersing techniques such as supercritical fluid technology, high speed electro-spinning and microenvironmental pH modified technology.
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OBJECTIVE: To prepare porous starch foam to improve the solubility and dissolution rate of dabigatran etexilate. METHODS: Porous starch foam (PSF) was synthesized as a carrier by solvent exchange method. Dabigatran etexilate (DE) was loaded onto the nanopores of PSF by solvent evaporation method. Scanning electron microscopy was used for investigating the morphology and structure of PSF. The dispersal state of DE in drug-loaded sample (PSF-DE) was determined by differential scanning calorimetry, powder X-ray diffraction and fourier transform infrared spectroscopy. The dissolution rate was measured by in-vitro dissolution experiment. RESULTS: Porous starch foam was prepared successfully and the spatial restriction of nanopores effectively suppressed crystal-linity of dabigatran etexilate as shown by structure characterization. The in-vitro dissolution experiment showed that the dissolution rate; of dabigatran etexilate was improved significantly. CONCLUSION: Porous starch foam can improve the hydrophilicity of the poorly water-soluble drug dabigatran etexilate.
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Objective To study the effect of surfactants on the dissolution profiles of poorly water-soluble acidic drug nimesulide from sustained-release tablets.Methods The anionic surfactant sodium dodecyl sulfate (SDS), cationic sur-factant cetyltrimethyl ammonium bromide (CTAB) and nonionic surfactant polysorbate 80 (Tween 80) were used to prepare nimesulide micelles .The effect of the buffer , surfactant and ionic strength on the equilibrium solubility of the drug and the in vitro release of sustained-release tablets was studied .Results and Conclusion In pH 1.2 HCl solution, water and pH 6.8 phosphate buffer, the solubilization capacity of CTAB was the highest.However, in pH 9.0 Tris buffer, when CTAB concen-tration was at about 1%, the equilibrium solubility of nimesulide was at the trough value .The in vitro release results were similar to those of equilibrium solubility and the kinetic pattern conformed to the first order equation according to the coefficient R .
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OBJECTIVE: To prepare amino-modified ordered mesoporous silica (NH2-OMS) as a drug carrier and test the loading and release properties of poorly water soluble drug carried by it. METHODS: OMS was first prepared using cetyltrimethyl ammonium bromide as the template and then modified by 3-aminopropyl trimethoxy silane to prepare NH2-OMS. N2 adsorption-desorption, X-ray diffraction and thermogravimetric analysis were used to characterize the NH2-OMS. Quercetin was loaded onto NH2-OMS in order to explore the drug loading properties of NH2-OMS. RESULTS: The drug loading and entrapment efficiency of quercetin-NH2-OMS were about 21.0% and 58.2%, respectively, when the concentration of quercetin was 4 mmol·L-1, the reaction time was 24 h and the temperature was set at 50°C. The in vitro release test demonstrated that quercetin-NH2-OMS could form supersaturated solution in simulated intestinal fluid and gastric fluid at concentrations of 13-fold and 27-fold of the thermodynamic solubility of quercetion. CONCLUSION: NH2-OMS, as the carrier for quercetin, can significantly increase its water solubility and release rate in intestinal and gastric fluids.