Producing Amorphous Solid Dispersions via Co-Precipitation and Spray Drying: Impact to Physicochemical and Biopharmaceutical Properties

Many small-molecule active pharmaceutical ingredients (APIs) exhibit low aqueous solubility and benefit from generation of amorphous dispersions of the API and polymer to improve their dissolution properties. Spray drying and hot-melt extrusion are 2 common methods to produce these dispersions; however, for some systems, these approaches may not be optimal, and it would be beneficial to have an alternative route. Herein, amorphous solid dispersions of compound A, a low-solubility weak acid, and copovidone were made by conventional spray drying and co-precipitation. The physicochemical properties of the 2 materials were assessed via X-ray diffraction, differential scanning calorimetry, thermal gravimetric analysis, and scanning electron microscopy. The amorphous dispersions were then formulated and tableted, and the performance was assessed in vivo and in vitro. In human dissolution studies, the co-precipitation tablets had slightly slower dissolution than the spray-dried dispersion, but both reached full release of compound A. In canine in vitro dissolution studies, the tablets showed comparable dissolution profiles. Finally, canine pharmacokinetic studies showed that the materials had comparable values for the area under the curve, bioavailability, and C_max. Based on the summarized data, we conclude that for some APIs, co-precipitation is a viable alternative to spray drying to make solid amorphous dispersions while maintaining desirable physicochemical and biopharmaceutical characteristics.     

HyperDSC studies of amorphous polyvinylpyrrolidone in a model wet granulation system

Measurements of the properties of amorphous materials are very important to help in the understanding of how materials behave during manufacture, storage and use of medicines. However, there are few methods that are suited to the study of amorphous materials, especially if in multi-component systems or model formulations. The goal here was to explore the potential for the use of HyperDSC to study a model granulation system. It was found that the sensitivity of HyperDSC was such that the glass transition (Tg) of polyvinylpyrrolidone (PVP) could be detected in granules made with realistic levels of this binder. The measured Tg in the granules, even after drying, was very different to that of PVP alone and to PVP in physical mixtures with lactose. It is argued that the granulation process has resulted in the dissolution of some lactose and that the amorphous binder holding the granules together is in fact a solid dispersion of PVP and lactose. Based on the standard Gordon-Taylor equation it was estimated that the solid dispersion contained 50% of PVP and lactose. Given that solid dispersions have a tendency to crystallise on storage, it could be expected that changes in the binder properties will occur with time after granulation. We believe that this is the first measurement of in situ properties of a binder in this way and opens the possibility of studies on formulated systems.     

Coprocessing of Nevirapine and Stavudine by Spray Drying

The objective of the present study was to coprocess 2 active pharmaceutical ingredients (APIs), nevirapine (NVP) and stavudine (STV), by spray drying technique to overcome the respective problems of poor solubility and poor content uniformity. The coprocessed product (NVP-STV CP) and untreated APIs were characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), particle size, surface area analysis, compressibility, and solubility. Coprocessing enhanced NVP solubility by ～1.5 fold and provided uniform distribution of low-dose STV in the formulation composite. Phase solubility studies elucidated the mechanism of enhanced NVP solubility. The coprocessed product was stable under accelerated stability conditions of 40°C/75% relative humidity (RH) for 3 months. The coprocessed product was formulated into 3 drug fixed dose combination (FDC) tablets with lamivudine (LMV), which gave an enhanced in vitro NVP drug release compared with the control formulation. Spray drying as a coprocessing technique optimally utilized the individual components of the antiretroviral FDC tablets and synergistically enhanced the performance attributes.     

Coprocessing of nevirapine and stavudine by spray drying

The objective of the present study was to coprocess 2 active pharmaceutical ingredients (APIs), nevirapine (NVP) and stavudine (STV), by spray drying technique to overcome the respective problems of poor solubility and poor content uniformity. The coprocessed product (NVP-STV CP) and untreated APIs were characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), particle size, surface area analysis, compressibility, and solubility. Coprocessing enhanced NVP solubility by approximately 1.5 fold and provided uniform distribution of low-dose STV in the formulation composite. Phase solubility studies elucidated the mechanism of enhanced NVP solubility. The coprocessed product was stable under accelerated stability conditions of 40 degrees C/75% relative humidity (RH) for 3 months. The coprocessed product was formulated into 3 drug fixed dose combination (FDC) tablets with lamivudine (LMV), which gave an enhanced in vitro NVP drug release compared with the control formulation. Spray drying as a coprocessing technique optimally utilized the individual components of the antiretroviral FDC tablets and synergistically enhanced the performance attributes.     

Properties of solid dispersions of piroxicam in polyvinylpyrrolidone.

Solid dispersions of piroxicam were prepared with polyvinylpyrrolidone (PVP) K-17 PF and PVP K-90 by solvent method. The physical state and drug:PVP interaction of solid dispersions and physical mixtures were characterized by X-ray diffraction, Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). FTIR analysis demonstrated the presence of intermolecular hydrogen bonding between piroxicam and PVP in solid dispersions. These interactions reflected the changes in crystalline structures of piroxicam. The amorphousness within the PVP moeity might be predicted in piroxicam dispersions by the disappearance of N-H or O-H peak of piroxicam. Dissolution studies indicated a significant increase in dissolution of piroxicam when dispersed in PVP. The better results were obtained with the lower molecular weight PVP K-17 than with higher molecular weight PVP K-90. The non-amorphous solid dispersions in PVP K-17 showed almost equally fast dissolution rates to amorphous dispersions in PVP K-90. The mechanism of dissolution of solid dispersion in PVP K-90 is predominantly diffusion-controlled due to the very high viscosity of PVP K-90. Dissolution was maximum with the amorphous solid dispersions containing drug:PVP K-17 1:5 and 1:6 which showed a 40-fold increase in dissolution in 5 min as compared with pure drug. Copyright     

Application of quartz crystal microbalance to study the impact of pH and ionic strength on protein-silicone oil interactions

The effect of adding a third polymer to immiscible binary solid dispersions was investigated. The model actives griseofulvin (GF), progesterone (PG) and phenindione (PD) were selected because they exemplify a key property of many poorly soluble molecules of having at least one hydrogen bonding acceptor moiety while not having any hydrogen bond donating moieties. Ternary solid dispersions of the drug, PVP (polyvinylpyrrolidone) (proton acceptor) and PHPMA (poly[2-hydroxypropyl methacrylate]) (proton acceptor and donor) were prepared by spray drying. Stability results showed that binary solid dispersions (API and PVP) of GF and PVP crystallized quickly while the amorphous form was not possible to prepare for PG and PD. The amorphous form was prolonged upon the incorporation of PHPMA in the solid dispersion (API, PHPMA and PVP). Based on measuring the melting points, the energy of mixing the drug with the polymer was calculated using the Flory-Huggins theory. The results showed that GF had the lowest free energy followed by PG and finally PD which agreed well with the stability results. These results suggest that the addition of a third polymer to immiscible binary solid dispersions can significantly improve the stability of the amorphous form.     

A Comparison of Spray-Drying and Co-Precipitation for the Generation of Amorphous Solid Dispersions (ASDs) of Hydrochlorothiazide and Simvastatin

Co-processing of APIs, the practice of creating multi-component APIs directly in chemical processing facilities used to make drug substance, is gaining increased attention with a view to streamlining manufacturing, improving supply chain robustness and accessing enhanced product attributes in terms of stability and bioavailability. Direct co-precipitation of amorphous solid dispersions (ASDs) at the final step of chemical processing is one such example of co-processing. The purpose of this work was to investigate the application of different advanced solvent-based processing techniques - direct co-precipitation (CP) and the benchmark well-established spray-drying (SD) process - to the production of ASDs comprised of a drug with a high T_g (hydrochlorothiazide, HCTZ) or a low T_g (simvastatin, SIM) molecularly dispersed in a PVP/VA 64 or Soluplus® matrix. ASDs of the same composition were manufactured by the two different methods and were characterised using powder X-ray diffraction (PXRD), modulated differential scanning calorimetry (mDSC), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and scanning electron microscopy (SEM). Both methods produced ASDs that were PXRD amorphous, with some differences, depending on the process used, in glass transition temperature and particle size distribution. Irrespective of manufacturing method used, all ASDs remained PXRD amorphous when subjected to high relative humidity conditions (75% RH, 25°C) for four weeks, although changes in the colour and physical characteristics were observed on storage for spray-dried systems with SIM and PVP/VA 64 copolymer. The particle morphology differed for co-precipitated compared to spray dried systems, with powder generated by the former process being comprised of more irregularly shaped particles of larger particle size when compared to the equivalent spray-dried systems which may enable more streamlined drug product processes to be used for CP materials. These differences may have implications in downstream drug product processing. A limitation identified when applying the solvent/anti-solvent co-precipitation method to SIM was the high antisolvent to solvent ratios required to effect the precipitation process. Thus, while similar outcomes may arise for both co-precipitation and spray drying processes in terms of ASD critical quality attributes, practical implications of applying the co-precipitation method and downstream processability of the resulting ASDs should be considered when choosing one solvent-based ASD production process over another.     

Physicochemical Characterization of Hot Melt Extruded Bicalutamide–Polyvinylpyrrolidone Solid Dispersions

Solid molecular dispersions of bicalutamide (BL) and polyvinylpyrrolidone (PVP) were prepared by hot melt extrusion technology at drug‐to‐polymer ratios of 1:10, 2:10, and 3:10 (w/w). The solid‐state properties of BL, physical mixtures of BL/PVP, and hot melt extrudates were characterized using differential scanning calorimetry (DSC), powder X‐ray diffractometry (PXRD), Raman, and Fourier transform infrared (FTIR) spectroscopy. Drug dissolution studies were subsequently conducted on hot melt extruded solid dispersions and physical mixtures. All hot melt extrudates had a single T_g between the T_g of amorphous BL and PVP indicating miscibility of BL with PVP and the formation of solid molecular dispersions. PXRD confirmed the presence of the amorphous form of BL within the extrudates. Conversely, PXRD patterns recorded for physical mixtures showed sharp bands characteristic of crystalline BL, whereas DSC traces had a distinct endotherm at 196°C corresponding to melting of crystalline BL. Further investigations using DSC confirmed solid‐state plasticization of PVP by amorphous BL and hence antiplasticization of amorphous BL by PVP. Experimentally observed T_g values of physical mixtures were shown to be significantly higher than those calculated using the Gordon–Taylor equation suggesting the formation of strong intermolecular interactions between BL and PVP. FTIR and Raman spectroscopy were used to investigate these interactions and strongly suggested the presence of secondary interaction between PVP and BL within the hot melt extrudates. The drug dissolution properties of hot melt extrudates were enhanced significantly in comparison to crystalline BL and physical mixtures. Moreover, the rate and extent of BL release were highly dependent on the amount of PVP present within the extrudate. Storage of the extrudates confirmed the stability of amorphous BL for up to 12 months at 20°C, 40% RH whereas stability was reduced under highly humid conditions (20°C, 65% RH). Interestingly, BL recrystallization after storage under these conditions had no effect on the dissolution properties of the extrudates. © 2009 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1322–1335, 2010     

Use of Spray-Dried Dispersions in Early Pharmaceutical Development: Theoretical and Practical Challenges

Spray-dried dispersions (SDDs) have become an important formulation technology for the pharmaceutical product development of poorly water-soluble (PWS) compounds. Although this technology is now widely used in the industry, especially in the early-phase development, the lack of mechanistic understanding still causes difficulty in selecting excipients and predicting stability of SDD-based drug products. In this review, the authors aim to discuss several principles of polymer science pertaining to the development of SDDs, in terms of selecting polymers and solvents, optimizing drug loading, as well as assessing physical stability on storage and supersaturation maintenance after dissolution, from both thermodynamic and kinetic considerations. In order to choose compatible solvents with both polymers and active pharmaceutical ingredients (APIs), a symmetric Flory-Huggins interaction (Δχ ～0) approach was introduced. Regarding spray drying of polymer-API solutions, low critical solution temperature (LCST) was discussed for setting the inlet temperature for drying. In addition, after being exposed to moisture, SDDs are practically converted to ternary systems with asymmetric Flory-Huggins interactions, which are thermodynamically not favored. In this case, the kinetics of phase separation plays a significant role during the storage and dissolution of SDD-based drug products. The impact of polymers on the supersaturation maintenance of APIs in dissolution media was also discussed. Moreover, the nature of SDDs, with reference to solid solution and the notion of solid solubility, was examined in the context of pharmaceutical application. Finally, the importance of robust analytical techniques to characterize the SDD-based drug products was emphasized, considering their complexity.     

Cefuroxime axetil solid dispersions prepared using solution enhanced dispersion by supercritical fluids

Cefuroxime axetil (CA) solid dispersions with HPMC 2910/PVP K-30 were prepared using solution enhanced dispersion by supercritical fluids (SEDS) in an effort to increase the dissolution rate of poorly water-soluble drugs. Their physicochemical properties in solid state were characterized by differential scanning calorimeter (DSC), powder X-ray diffraction (PXRD), Fourier transform infrared spectrometry (FT-IR) and scanning electron microscopy. No endothermic and characteristic diffraction peaks corresponding to CA were observed for the solid dispersions in DSC and PXRD. FTIR analysis demonstrated the presence of intermolecular hydrogen bonds between CA and HPMC 2910/PVP K-30 in solid dispersions, resulting in the formation of amorphous or non-crystalline CA. Dissolution studies indicated that the dissolution rates were remarkably increased in solid dispersions compared with those in the physical mixture and drug alone. In conclusion, an amorphous or non-crystalline CA solid dispersion prepared using SEDS could be very useful for the formulation of solid dosage forms.     

Using Acetone/Water Binary Solvent to Enhance the Stability and Bioavailability of Spray Dried Enzalutamide/HPMC-AS Solid Dispersions

We demonstrated a facile approach, by adjusting the solvent ratio of water/acetone binary mixture, to alter the intermolecular interactions between Enzalutamide (ENZ) and hydroxypropyl methylcellulose acetate succinate (HPMC-AS) for spray drying process, which can be readily implemented to produce spray-dried dispersions (SDD) with enhanced stability and bioavailability. The prepared SDD of ENZ/HPMC-AS were examined systematically in terms of particle size, morphology, dissolution, solubility, stability, and bioavailability. Our results show that the introduction of water (up to 30% volume fraction) can effectively reduce the hydrodynamic diameter of HPMC-AS from approximately 220 nm to 160 nm (a reduction of c.a. 20%), which increases the miscibility of the drug and polymer, delaying or inhibiting the crystallization of ENZ during the spray drying process, resulting in a homogeneous amorphous phase. The benefits of using acetone/water binary mixture were subsequently evidenced by an increased specific surface area, improved dissolution profile and relative bioavailability, enhanced stability, and elevated drug release rate. This fundamental finding underpins the great potential of using binary mixture for spray drying process to process active pharmaceutical ingredients (APIs) that are otherwise challenging to handle.     

Preparation, characterization and in vitro dissolution of aceclofenac-loaded PVP solid dispersions prepared by spray drying or rotary evaporation method

This study was conducted to enhance dissolution rate of aceclofenac (ACF) with extremely low solubility and high permeability (BCS class II) in water using poly vinyl pyrrolidone (PVP) and sodium lauryl sulfate as carriers. Solid dispersions were prepared by spray drying method and rotary evaporation method using different ratios of ACF and polymers. The characterization of solid dispersions was evaluated by scanning electron microscopy, Fourier transformation infrared spectroscopy, differential scanning calorimetry and powder X-ray diffractometer. The dissolution behavior of solid dispersions was compared with pure ACF (API) and Airtal^® (Deawoong, Co, Korea) as control groups in simulated phosphate buffer at pH 6.8. The dissolution rate of the drug was affected by nature and amount of polymer used. The prepared solid dispersion of ACF/PVP (1:5) appeared to have the highest dissolution rate. Therefore, solid dispersion techniques of spray drying and rotary evaporation method can be successfully used for the enhancement of the dissolution rate of ACF.     

Water vapor absorption into amorphous hydrophobic drug/poly(vinylpyrrolidone) dispersions

Water vapor absorption isotherms were measured for three amorphous hydrophobic drug/poly(vinylpyrrolidone) (PVP) dispersions in the concentration range 10-90% w/w PVP. Experimental isotherms were compared to predicted isotherms calculated using each individual component isotherm multiplied by its weight fraction. Indomethacin (IMC)/PVP, ursodeoxycholic acid (UDCA)/PVP and indapamide (IDP)/PVP amorphous dispersions all exhibited experimental isotherms reduced relative to predicted isotherms indicating that dispersion formation altered the water vapor absorption properties of the individual components. For all three drug/PVP systems, deviation from predicted water uptake was greatest close to the 1:1 drug:PVP monomer composition, indicating that intermolecular interaction in amorphous dispersions affects the water uptake properties of the individual components. Using dry glass transition temperature (T(g)) data, the extent of drug/PVP interaction was shown to be greatest in the IDP/PVP system, which could explain why the largest reduction in water vapor absorption was found in this system. The plasticizing effect of absorbed water varied according to dry dispersion PVP content in all systems and the resulting nonideal changes in free volume, calculated using the Vrentas model, were greatest close to the 1:1 drug:PVP monomer composition. A three-component Flory-Huggins model successfully predicted isotherms for IMC/PVP compositions from 60 to 90% w/w PVP and identified an IMC-PVP interaction parameter chi in the range 1.27-1.49, values that suggest poor homogeneity of mixing in the dry system. These data indicate that amorphous dispersion formation causes both chemical and physical changes in the individual amorphous components that can have a significant effect on their water vapor absorption properties.     

Formation and characterization of solid dispersions of piroxicam and polyvinylpyrrolidone using spray drying and precipitation with compressed antisolvent

Solid dispersions of a poorly water-soluble drug piroxicam in polyvinylpyrrolidone (PVP) were prepared by precipitation with compressed antisolvent (PCA) and spray drying techniques. Physicochemical properties of the products and drug-polymer interactions were characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, and differential scanning calorimetry, etc. Piroxicam was found amorphously dispersed in both solid dispersion systems with the drug to polymer weight ratio of 1:4. Spectra data indicated the formation of hydrogen bonding between the drug and the polymer. Both techniques evaluated in this work resulted in improved dissolution of piroxicam. By comparison, PCA-processed solid dispersions showed distinctly superior performance in that piroxicam dissolved completely within the first 5 min and the dissolution rate was at least 20 times faster than raw drug did within the first 15 min. PCA processing could provide an effective pharmaceutical formulation technology to improve the bioavailability of poorly water-soluble drug.     

An Investigation into the Effect of Spray Drying Temperature and Atomizing Conditions on Miscibility,Physical Stability,and Performance of Naproxen–PVP K 25 Solid Dispersions

The present study investigates the effect of changing spray drying temperature (40°C–120°C) and/or atomizing airflow rate (AR; 5–15 L/min) on the phase structure, physical stability, and performance of spray-dried naproxen–polyvinylpyrrolidone (PVP) K25 amorphous solid dispersions. The modulated differential scanning calorimetry, attenuated total internal reflectance-Fourier transform infrared, and powder X-ray diffractometry (pXRD) studies revealed that higher inlet temperature (IT) or atomization airflow leads to the formation of amorphous-phase-separated dispersions with higher strongly H-bonded and free PVP fractions, whereas that prepared with the lowest IT was more homogeneous. The dispersion prepared with the lowest atomization AR showed trace crystallinity. Upon exposure to 75% relative humidity (RH) for 3 weeks, the phase-separated dispersions generated by spray drying at higher temperature or higher atomization airflow retained relatively higher amorphous drug fraction compared with those prepared at slow evaporation conditions. The humidity-controlled pXRD analysis at 98% RH showed that the dispersion prepared with highest atomization AR displayed the slowest kinetics of recrystallization. The molecular-level changes occurring during recrystallization at 98% RH was elucidated by spectroscopic monitoring at the same humidity. The rate and extent of the drug dissolution was the highest for dispersions prepared at the highest atomizing AR and the lowest for that prepared with the slowest atomizing condition.     

槲皮素PVP固体分散体的制备及物相鉴定

目的用溶剂法制备槲皮素-PVP固体分散体并考察其溶出特性并对物相进行鉴定。方法采用溶剂法制备槲皮素-PVP固体分散体,通过溶出实验对槲皮素溶出率的测定研究固体分散体的溶出性质,利用差热分析（Differentialscanning calorimetry,DSC）、红外光谱分析（Infrared spectroscopy,IR）、粉末X衍射（X-ray powder diffractometry,PXRD）、扫描电镜（Scanning electron microscopy,SEM）等方法对其进行物相鉴定。结果槲皮素-PVP固体分散体的溶出速率相对其物理混合物有了明显的改善; 溶解实验显示固体分散体中槲皮素的溶解度有了显著的提高;热差分析及粉末X衍射结果表明固体分散体中槲皮素呈非结晶形式;扫描电镜下固体分散体中无槲皮素晶体。结论采用溶剂法制备槲皮素-PVP固体分散体可显著提高槲皮素的溶解度及溶出速度。     

Predicting the physical state of spray dried composites: salbutamol sulphate/lactose and salbutamol sulphate/polyethylene glycol co-spray dried systems

The effect of spray drying salbutamol sulphate, salbutamol sulphate/lactose and salbutamol sulphate/polyethylene glycol (PEG) solutions was investigated. Co-spray drying salbutamol sulphate with lactose, which is amorphous when spray dried alone, resulted in amorphous composites. Co-spray drying salbutamol sulphate with PEG 4000 and PEG 20,000, which do not form amorphous systems when spray dried alone, resulted in systems of varying crystallinity, the crystallinity depending on the weight ratio of polymer to drug. Examination of the physical properties of these salbutamol sulphate co-spray dried systems and those of bendroflumethiazide/PEG and lactose/PEG composites suggested that the formation and physical stability of amorphous composites prepared by spray drying is dependent on whether the glass transition temperature, Tg, of one of the two components is high enough to result in a Tg of the composite sufficiently high that the Kauzmann temperature of the mix is greater than the temperature of storage. The modified Gordon-Taylor equation proved to be useful in predicting the likelihood that a two-component composite will be amorphous on spray drying. Furthermore, the Gordon-Taylor equation was also useful in predicting the likely physical stability of amorphous two component composites and predicted that even polymers with apparently low Tgs, such as PEGs, may be stabilised in an amorphous composite by a suitable additive having a sufficiently high Tg.     

Silymarin-solid dispersions: characterization and influence of preparation methods on dissolution

The influence of preparation methodology of silymarin solid dispersions using a hydrophilic polymer on the dissolution performance of silymarin was investigated. Silymarin solid dispersions were prepared using HPMC E 15LV by kneading, spray drying and co-precipitation methods and characterized by FTIR, DSC, XRPD and SEM. Dissolution profiles were compared by statistical and model independent methods. The FTIR and DSC studies revealed weak hydrogen bond formation between the drug and polymer, while XRPD and SEM confirmed the amorphous nature of the drug in co-precipitated solid dispersion. Enhanced dissolution compared to pure drug was found in the following order: co-precipitation > spray drying > kneading methodology (p < 0.05). All preparation methods enhanced silymarin dissolution from solid dispersions of different characteristics. The co-precipitation method proved to be best and provided a stable amorphous solid dispersion with 2.5 improved dissolution compared to the pure drug.     

Anomalous properties of spray dried solid dispersions

The use of solid dispersions for oral dosage forms can increase the dissolution rate of poorly soluble drugs. Spray drying is one process that can be used to prepare solid dispersions. Spray dried solid dispersions of griseofulvin, poly[N-(2-hydroxypropyl)methacrylate] (PHPMA) and polyvinylpyrrolidone (PVP) were prepared from acetone and water. When methanol was substituted for water, the morphology, stability and dissolution properties of the solid dispersion changed dramatically. The glass transition temperature for the ternary solid dispersion (GF, PHPMA, and PVP) shifted from 83°C (acetone/water) to 103°C for the acetone/methanol system. These differences in the dispersions are thought to derive from conformational variations of the polymers in solution prior to spray drying. Both PHPMA and PVP formed globules in solution of a size range between 16 and 33 nm. The effect of drug and polymer concentration in solution (before spray drying) on the properties of the solid dispersion was studied. It was found that solid dispersions that were prepared using lower concentrations of drug and polymers in solutions resulted in the formation of particles that display a lower relaxation rate. This result supports the hypothesis that the polymer conformation may significantly change the properties of the solid dispersion. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4724–4737, 2009     

他达那非固体分散体的制备和性质研究

目的制备他达那非(tadalafil,TD)固体分散体并进行性质研究。方法利用喷雾干燥法制备固体分散体,以表观溶解度和溶出度为指标筛选处方,采用差示扫描量热(DSC)、粉末X-射线衍射(PXRD)和接触角测定等技术研究药物的存在状态和润湿性等理化性质。结果固体分散体将他达那非的表观溶解度提高22.6倍;20min内药物的累积溶出超过90%;固体分散体药物以分子或无定形状态存在;接触角减小,润湿性增大。结论采用十二烷基硫酸钠(SDS)和介孔硅为载体制备的他达那非固体分散体,能明显提高药物的表观溶解度和溶出度。