A comparative study of spray-dried and freeze-dried hydrocortisone/polyvinyl pyrrolidone solid dispersions

Poor water solubility of new chemical entities (NCEs) is one of the major challenges the pharmaceutical industry currently faces. The purpose of this study was to investigate the feasibility of freeze-drying as an alternative technique to spray-drying to produce solid dispersions of poorly water-soluble drugs. Also investigated was the use of aqueous solvent mixtures in place of pure solvent for the production of solid dispersions. Aqueous solvent systems would reduce the environmental impact of pure organic solvent systems. Spray-dried and freeze-dried hydrocortisone/polyvinyl pyrrolidone solid dispersions exhibited differences in dissolution behavior. Freeze-dried dispersions exhibited faster dissolution rates than the corresponding spray-dried dispersions. Spray-dried systems prepared using both solvent systems (20% v/v and 96% v/v ethanol) displayed similar dissolution performance despite displaying differences in glass transition temperatures (T(g)) and surface areas. All dispersions showed drug/polymer interactions indicated by positive deviations in T(g) from the predicted values calculated using the Couchman-Karasz equation. Fourier transform infrared (FTIR) spectroscopic results confirmed the conversion of crystalline drug to the amorphous in the dispersions. Stability studies were preformed at 40°C and 75% relative humidity to investigate the physical stability of prepared dispersions. Recrystallization was observed after a month and the resultant dispersions were tested for their dissolution performance to compare with the dissolution performance of the dispersions prior to the stability study. The dissolution rate of the freeze-dried dispersions remained higher than both spray-dried dispersions after storage.     

Solubility and dissolution performances of spray-dried solid dispersion of Efavirenz in Soluplus

Abstract

Efavirenz (EFV), a first-line anti-HIV drug largely used as part of antiretroviral therapies, is practically insoluble in water and belongs to BCS class II (low solubility/high permeability). The aim of this study was to improve the solubility and dissolution performances of EFV by formulating an amorphous solid dispersion of the drug in polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol graft copolymer (Soluplus^®) using spray-drying technique. To this purpose, spray-dried dispersions of EFV in Soluplus^® at different mass ratios (1:1.25, 1:7, 1:10) were prepared and characterized using particle size measurements, SEM, XRD, DSC, FTIR and Raman microscopy mapping. Solubility and dissolution were determined in different media. Stability was studied at accelerated conditions (40?°C/75% RH) and ambient conditions for 12 months. DSC and XRD analyses confirmed the EFV amorphous state. FTIR spectroscopy analyses revealed possible drug–polymer molecular interaction. Solubility and dissolution rate of EFV was enhanced remarkably in the developed spray-dried solid dispersions, as a function of the polymer concentration. Spray-drying was concluded to be a proper technique to formulate a physically stable dispersion of amorphous EFV in Soluplus^®, when protected from moisture.     

Nimodipine (NM) tablets with high dissolution containing NM solid dispersions prepared by hot-melt extrusion

Using a mixture of Eudragit^® EPO and polyvinylpyrrolidone/vinyl acetate copolymer (PVP/VA) (Kollidon VA64) as carriers, a nimodipine solid dispersion (NM-SD) was prepared by hot-melt extrusion (HME) to achieve high dissolution. The dissolution profiles in 900?mL 0.1?mol/L HCl showed that the drug release of NM-SD reached 90% in 1?h. Powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) were used to characterize the state of NM. The results obtained showed that NM was in an amorphous form in the solid dispersion (SD). NM-SD tablets (NM-T-SD) were compressed by wet granulation and direct compression, respectively. The stability of NM-T-SD was examined during a 2-month storage period (40°C, RH 75%). The results showed that the dissolution of NM-T-SD was slightly reduced after 2 months storage (40°C, RH 75%), which implied that aging occurred to some degree. However, no NM crystals could be observed by PXRD after 2 months storage for NM-T-SD (F₁₁) prepared by direct compression.     

Increased dissolution rates of tranilast solid dispersions extruded with inorganic excipients

The purpose of this study was to evaluate the performance of Neusilin® (NEU) a synthetic magnesium aluminometasilicate as an inorganic drug carrier co-processed with the hydrophilic surfactants Labrasol and Labrafil to develop Tranilast (TLT)-based solid dispersions using continuous melt extrusion (HME) processing. Twin-screw extrusion was optimized to develop various TLT/excipient/surfactant formulations followed by continuous capsule filling in the absence of any downstream equipment. Physicochemical characterization showed the existence of TLT in partially crystalline state in the porous network of inorganic NEU for all extruded formulations. Furthermore, in-line NIR studies revealed a possible intermolecular H-bonding formation between the drug and the carrier resulting in the increase of TLT dissolution rates. The capsules containing TLT-extruded solid dispersions showed enhanced dissolution rates and compared with the marketed Rizaben^® product.     

Dissolution and precipitation behavior of ternary solid dispersions of ezetimibe in biorelevant media

Abstract

The effects of different formulations and processes on inducing and maintaining the supersaturation of ternary solid dispersions of ezetimibe (EZ) in two biorelevant media fasted-state simulated intestinal fluid (FaSSIF) and fasted-state simulated gastric fluid (FaSSGF) at different temperatures (25?°C and 37?°C) were investigated in this work.

Ternary solid dispersions of EZ were prepared by adding polymer PVP-K30 and surfactant poloxamer 188 using melt-quenching and spray-drying methods. The resulting solid dispersions were characterized using scanning electron microscopy, differential scanning calorimetry (DSC), modulated DSC, powder X-ray diffraction and Fourier transformation infrared spectroscopy. The dissolution of all the ternary solid dispersions was tested in vitro under non-sink conditions.

All the prepared solid dispersions were amorphous in nature. In FaSSIF at 25?°C, the melt-quenched (MQ) solid dispersions of EZ were more soluble than the spray-dried (SD) solid dispersions and supersaturation was maintained. However, at 37?°C, rapid and variable precipitation behavior was observed for all the MQ and SD formulations. In FaSSGF, the melting method resulted in better solubility than the spray-drying method at both temperatures.

Ternary solid dispersions show potential for improving solubility and supersaturation. However, powder dissolution experiments of these solid dispersions of EZ at 25?°C may not predict the supersaturation behavior at physiologically relevant temperatures.     

Formulation and pharmacokinetics of gelucire solid dispersions of flurbiprofen

Context: Development of solid dispersions is to improve the therapeutic efficacy by increasing the drug solubility, dissolution rate, bioavailability as well as to attain rapid onset of action.

Objective: The present research deals with the development of solid dispersions of flurbiprofen which is poorly water soluble to improve the solubility and dissolution rate using gelucires.

Materials and methods: In this study, solid dispersions were prepared following solvent evaporation method using gelucire 44/14 and gelucire 50/13 as carriers in different ratios. Then the formulations were evaluated for different physical parameters, solubility studies, DSC, FTIR studies and in vitro dissolution studies to select the best formulation that shows rapid dissolution rate and finally subjected to pharmacokinetic studies.

Results and discussion: From the in vitro dissolution study, formulation F3 showed the better improvement in solubility and dissolution rate. From the pharmacokinetic evaluation, the control tablets produced peak plasma concentration (C_max) of 9140.84?±?614.36?ng/ml at 3?h T_max and solid dispersion tablets showed C_max?=?11?445.46?±?149.23?ng/ml at 2?h T_max. The area under the curve for the control and solid dispersion tablets was 31?495.16?±?619.92 and 43?126.52?±?688.89?ng h/ml and the mean resident time was 3.99 and 3.68?h, respectively.

Conclusion: From the above results, it is concluded that the formulation of gelucire 44/14 solid dispersions is able to improve the solubility, dissolution rate as well as the absorption rate of flurbiprofen than pure form of drug.     

Formulation and optimization of spray-dried amlodipine solid dispersion for enhanced oral absorption

Objective: To enhance the oral absorption of photosensitive amlodipine free base, which exhibits a slow dissolution rate and low permeability characteristics, an amorphous solid dispersion system was formulated and characterized.

Material and methods: The solid dispersion was prepared by dispersing the amlodipine free base in excess dextrin (1:10 by weight) using a spray-drying technique in the presence of a minimum amount (0.9% w/w) of SLS as an absorption enhancer. The dextrin-based solid dispersion of amlodipine (Amlo-SD) was evaluated in term of formulation, characterization and in vivo absorption study, as well as the spray-drying process was also optimized.

Results and discussion: The Amlo-SD particles were spherical with a smooth surface and an average particle size of 12.9 μm. Amlodipine was dispersed in an amorphous state and its content remained uniform in the Amlo-SD. The physicochemical stability of the Amlo-SD was maintained at room temperature for 6 months and the photostability was considerably improved. The dissolution of the Amlo-SD was much faster than that of amlodipine at pH 1.2 and 6.8. Amlo-SD produced significantly higher plasma concentrations of amlodipine in rats than amlodipine alone. Amlo-SD with and without SLS provided 2.8- and 2.0-fold increase in AUC, respectively: the difference seems to be attributed to a permeability enhancement effect by SLS.

Conclusion: The Amlo-SD with SLS system is a potential formulation option for amlodipine.     

Corroboration of naringin effects on the intestinal absorption and pharmacokinetic behavior of candesartan cilexetil solid dispersions using in-situ rat models

Objective: The aim of this study was to corroborate the effects of naringin, a P-glycoprotein inhibitor, on the intestinal absorption and pharmacokinetics of candesartan (CDS) from candesartan cilexetil (CAN) solid dispersions using in-situ rat models.

Materials and methods: Intestinal transport and absorption studies were examined by in-situ single pass perfusion and closed-loop models. We evaluated the intestinal membrane damage in the presence of naringin by measuring the release of protein and alkaline phosphatase (ALP).

Results and discussion: We noticed 1.47-fold increase in P_eff of CDS from freeze-dried CAN-loaded solid dispersions with naringin (15?mg/kg, w/w) when compared with freeze-dried solid dispersion without naringin using in-situ single pass intestinal perfusion model. However, no intestinal membrane damage was observed in the presence of naringin. Our findings from in-situ closed-loop pharmacokinetic studies showed 1.34-fold increase in AUC with elevated C_max and shortened t_max for freeze-dried solid dispersion with naringin as compared to freeze-dried solid dispersion without naringin.

Conclusion: This study demonstrated that increased solubilization (favored by freeze-dried solid dispersion) and efflux pump inhibition (using naringin), the relative bioavailability of CDS can be increased, suggesting an alternative potential for improving oral bioavailability of CAN.     

Classification of solid dispersions: correlation to (i) stability and solubility (ii) preparation and characterization techniques

Solid dispersion has been a topic of interest in recent years for its potential in improving oral bioavailability, especially for poorly water soluble drugs where dissolution could be the rate-limiting step of oral absorption. Understanding the physical state of the drug and polymers in solid dispersions is essential as it influences both the stability and solubility of these systems. This review emphasizes on the classification of solid dispersions based on the physical states of drug and polymer. Based on this classification, stability aspects such as crystallization tendency, glass transition temperature (T_g), drug polymer miscibility, molecular mobility, etc. and solubility aspects have been discussed. In addition, preparation and characterization methods for binary solid dispersions based on the classification have also been discussed.     

Influence of different polymers on crystallization tendency and dissolution behavior of cilnidipine in solid dispersions

Context: Cilnidipine (CN) is a novel dihydropyridine calcium antagonist that is practically insoluble in aqueous media and exhibits a low oral bioavailability or limited clinical efficacy.

Objective: This study investigated the effects of three commercial and chemically diverse polymers – PVP, PVP/VA and Soluplus – on crystallization tendency and in vitro dissolution profiles of CN in order to determine an optimum carrier for composing the preferred solid dispersion (SD) of CN.

Methods: All these co-evaporated systems were characterized up to 3 months by thermoanalytical (DSC), crystallographic (POM, PXRD), microscopic (SEM) and spectroscopic (FTIR) techniques.

Results: The results showed that the polymers could be sorted by their effects of inhibiting CN crystallization in the ascending order: Soluplus, PVP/VA, PVP. The sequence was in accordance with that of the strength of drug–polymer hydrogen bonds revealed by FTIR spectra. It could be ascribed to relative hydrogen-bonding acceptor strengths of N-vinylpyrrolidone moiety in the polymer molecules. On the other hand, all the SDs showed enhanced dissolution profiles compared to pure CN alone. On their effects of enhancing CN dissolution, the polymers could be sorted in the descending order: Soluplus, PVP, PVP/VA.

Conclusions: It implied that the dissolution behavior of CN could bear a close relationship to both hydration capacity and hydrogen-bonding interaction tendency of moieties of the polymers. It might suggest an optimal formulation for CN comprising both PVP and Soluplus.     

Spray-dried solid dispersions containing ferulic acid: comparative analysis of three carriers,in vitro dissolution,antioxidant potential and in vivo anti-platelet effect

This article aimed to improve the relative solubility and dissolution rate of ferulic acid (FA) by the use of spray-dried solid dispersions (SDs) in order to ensure its in vitro antioxidant potential and to enhance its in vivo anti-platelet effect. These SDs were prepared by spray-drying at 10 and 20% of drug concentration using polyvinylpyrrolidone K30 (PVP-K30), polyethylene glycol 6000 (PEG 6000) and poloxamer-188 (PLX-188) as carriers. SDs and physical mixtures (PM) were characterized by SEM, XRPD, FTIR spectroscopy and TGA analysis. Spray-dried SDs containing FA were successfully obtained. Relative solubility of FA was improved with increasing carrier concentration. PVP-K30 and PEG 6000 formulations showed suitable drug content values close to 100%, whereas PLX-188 presented mean values between 70 and 90%. Agglomerates were observed depending on the carrier used. XRPD patterns and thermograms indicated that spray-drying led to drug amorphization and provided appropriate thermal stability, respectively. FTIR spectra demonstrated no remarkable interaction between carrier and drug for PEG 6000 and PLX-188 SDs. PVP-K30 formulations had changes in FTIR spectra, which denoted intermolecular O–H???O?=?C bonds. Spray-dried SDs played an important role in enhancing dissolution rate of FA when compared to pure drug. The free radical-scavenging assay confirmed that the antioxidant activity of PEG 6000 10% SDs was kept. This formulation also provided a statistically increased in vivo anti-platelet effect compared to pure drug. In summary, these formulations enhanced relative solubility and dissolution rate of FA and chosen formulation demonstrated suitable in vitro antioxidant activity and improved in vivo anti-platelet effect.     

Effects of preparing techniques and aging on dissolution behavior of the solid dispersions of NF/Soluplus/Kollidon SR: identification and classification by a combined analysis by FT-IR spectroscopy and computational approaches

Context: Pharmaceutical solid dispersions are known to be seriously affected by issues of aging and processing.

Objective: This study investigated the spectral patterns in the solid dispersions (SD) of Nifedipine/Soluplus/Kollidon SR and the feasibility of the methodology in identification and evaluation of the solid dispersions.

Methods: The SD samples were prepared by hot melt extrusion (HMESD), solvent-evaporation (SESD), and fusion-cooling (FCSD). In order to distinguish the different SD samples, a combined analytical strategy by FT-IR spectrum, Raman spectrum, and computational approaches (PCA and HCA) were developed to investigate the spectral patterns of the solid dispersions. Differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), scanning electron microscope (SEM), and dissolution test were employed as the reference characterization. The stability test under the accelerated condition was carried out to investigate the physical stability of the SDs.

Result: For the three prepared SDs, the evident differences on the dissolution behaviors and the trend of aging was observed. By means of the combined analytical strategy, the samples could be successfully identified in terms of their preparing techniques. The strength of hydrogen bonding interaction between NF and polymers decreased in the order of HMESD?>?SESD?>?FCSD. The results of the stability test indicated that the similarity factor f₂ value of dissolution profile decreased in the order of HMESD?>?SESD?>?FCSD. HMESD exhibited a tendency of minimal changing on both dissolution behavior and spectral patterns.

Conclusion: The combined strategy suggested the possibility for identification of specific SDs in quality control and prediction of their trends on the aging.     

A comprehensive understanding of lowly-hydrolyzed polyvinyl alcohol-based ternary solid dispersions with the use of a combined mixture-process design

Abstract

We recently reported lowly hydrolyzed polyvinyl alcohol (L-PVA, 70–74% hydrolyzed, about 580 polymerized, JR-05) as a promising matrix for hot-melt extrusion (HME) due to its unique micelle formation ability compared to the most commonly used PVA (87–89% hydrolyzed, about 580 polymerized). In the present study, we focused on the effect of composition [indomethacin (IND), L-PVA, sorbitol] and process parameters (temperature and screw speed) on each response, i.e. processing torque, and physicochemical properties such as residual crystallinity, residual ratio, and area under the dissolution curve (AUDC) in supersaturated solution using a HME by applying the design of experiment (DoE) approach. To overcome the poor processability of L-PVA, given its semicrystalline nature, we applied sorbitol as a plasticizer and systematically and simultaneously evaluated its influence on the outputs based on the mixture design combined with process factors. Few studies have focused on comprehensive evaluation of the composition and HME process conditions because obtaining a design space requires numerous experiments. We found that incorporating sorbitol into the L-PVA greatly improved the processing torque. However, sorbitol negatively influenced the degree of residual crystallinity and the AUDC of IND. Lastly, we established a laboratory-scale design space that could achieve high supersaturation and ensure adequate miscibility between each component, using an acceptable processing torque for HME, by applying the minimum amount of sorbitol. These fundamental results suggest that sorbitol maximizes the potency of L-PVA as a carrier in HME.     

Preparation and characterization of Simvastatin solid dispersion using skimmed milk

Simvastatin has low aqueous solubility resulting in low oral bioavailability (5%) and thus presents a challenge in formulating a suitable dosage form. To improve the aqueous solubility, a solid dispersion formulation of Simvastatin was prepared by lyophilization utilizing skimmed milk as a carrier. Six different formulations were prepared with varying ratios of drug and carrier and the corresponding physical mixtures were also prepared. The improvement of amorphous state through solid dispersion was confirmed by differential scanning calorimetry and X-ray diffraction studies. The optimum drug-to-carrier ratio of 1:9 enhanced solubility nearly 30-fold as compared to pure drug. In-vitro drug release studies exhibited a cumulative release of 86.69% as compared to 25.19% for the pure drug. Additionally, scanning electron microscopy studies suggested the conversion of crystalline Simvastatin to an amorphous form. In a Triton-induced hyperlipidemia model, a 3-fold increase in the lipid lowering potential was obtained with the reformulated drug as compared to pure drug. These results suggest that solid dispersion of Simvastatin using skimmed milk as carrier is a promising approach for oral delivery of Simvastatin.     

Characterization of solid dispersions of Patchouli alcohol with different polymers: effects on the inhibition of reprecipitation and the improvement of dissolution rate

Solid dispersion technique is known to be an effective approach for the polymer to keep drugs stable in the solid state, thereby improving the dissolution rate and oral bioavailability through inhibiting reprecipitation in supersaturated solution. In this study, to evaluate the inhibitory effect of polyethylene glycol-6000 (PEG), Polyvinylpyrrolidone K30 (PVP) and Aminoalkyl methacrylate copolymer (Eudragit), the reprecipitation profiles were observed from supersaturated solutions of Patchouli alcohol (PA) in the presence and absence of the polymers. Furthermore, the dissolution profiles of PA solid dispersions formulated with PEG, PVP or Eudragit were compared for investigating the effect on improving dissolution of each polymer. Solid dispersions formulated with Eudragit were found to result in solution with the highest extent of supersaturation. By contrast, PEG and PVP were less effective. At equivalent supersaturation, all three polymers are capable of mitigating reprecipitation relative to that of PA alone. In addition, in the PA solid dispersion with Eudragit (E-SD (1/3)), the highest concentration of supersaturation of PA was maintained for prolonged time. These results unambiguously indicate that it is imperative to select the appropriate polymer and drug/polymer ratio in addition to considering the stability of the supersaturated solution, which was generated following dissolution of amorphous solid dispersion.     

Dissolution rate enhancement,in vitro evaluation and investigation of drug release kinetics of chloramphenicol and sulphamethoxazole solid dispersions

Formulation of solid dispersions is one of the effective methods to increase the rate of solubilization and dissolution of poorly soluble drugs. Solid dispersions of chloramphenicol (CP) and sulphamethoxazole (SX) as model drugs were prepared by melt fusion method using polyethylene glycol 8000 (PEG 8000) as an inert carrier. The dissolution rate of CP and SX were rapid from solid dispersions with low drug and high polymer content. Characterization was performed using fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). FTIR analysis for the solid dispersions of CP and SX showed that there was no interaction between PEG 8000 and the drugs. Hyper-DSC studies revealed that CP and SX were converted into an amorphous form when formulated as solid dispersion in PEG 8000. Mathematical analysis of the release kinetics demonstrated that drug release from the various formulations followed different mechanisms. Permeability studies demonstrated that both CP and SX when formulated as solid dispersions showed enhanced permeability across Caco-2 cells and CP can be classified as well-absorbed compound when formulated as solid dispersions.     

Preparation of amorphous solid dispersions by rotary evaporation and KinetiSol Dispersing: approaches to enhance solubility of a poorly water-soluble gum extract

Acetyl-11-keto-β-boswellic acid (AKBA), a gum resin extract, possesses poor water-solubility that limits bioavailability and a high melting point making it difficult to successfully process into solid dispersions by fusion methods. The purpose of this study was to investigate solvent and thermal processing techniques for the preparation of amorphous solid dispersions (ASDs) exhibiting enhanced solubility, dissolution rates and bioavailability. Solid dispersions were successfully produced by rotary evaporation (RE) and KinetiSol® Dispersing (KSD). Solid state and chemical characterization revealed that ASD with good potency and purity were produced by both RE and KSD. Results of the RE studies demonstrated that AQOAT®-LF, AQOAT®-MF, Eudragit® L100-55 and Soluplus with the incorporation of dioctyl sulfosuccinate sodium provided substantial solubility enhancement. Non-sink dissolution analysis showed enhanced dissolution properties for KSD-processed solid dispersions in comparison to RE-processed solid dispersions. Variances in release performance were identified when different particle size fractions of KSD samples were analyzed. Selected RE samples varying in particle surface morphologies were placed under storage and exhibited crystalline growth following solid-state stability analysis at 12 months in comparison to stored KSD samples confirming amorphous instability for RE products. In vivo analysis of KSD-processed solid dispersions revealed significantly enhanced AKBA absorption in comparison to the neat, active substance.     

Selection of excipient,solvent and packaging to optimize the performance of spray-dried formulations: case example fenofibrate

Context: Along with other options, solid dispersions prepared by spray drying offer the possibility of formulating poorly soluble drugs in a rapidly dissolving format. As a wide range of potential excipients and solvents is available for spray drying, it is usually necessary to carry out a comprehensive array of studies to arrive at an optimal formulation.

Objective: To study the influence of formulation parameters such as co-sprayed excipients, solvents and packaging on the manufacture, in vitro performance and stability of spray-dried oral drug products using fenofibrate as a model drug.

Materials and methods: Solid dispersions of fenofibrate with different amorphous polymers were manufactured from two solvent systems by spray drying. These were characterized in terms of physicochemical properties, crystalline content and dissolution behavior in biorelevant media upon production and after storage in two packaging systems (Glass and Activ-Vials^?).

Results and discussion: Spray drying the same formulation from two different solvents led to different physicochemical properties, dissolution behavior and long-term stability. The dissolution behavior and long-term stability also varied significantly among excipients. The viscosity of the polymer and the packaging material proved to be important to the long-term stability.

Conclusion: For spray-dried products containing fenofibrate, the excipients were ranked according to dissolution and stability performance as follows: PVP derivatives >> HPMC 2910/15, HPMCAS-MF, HP-β-CD >> PVP:PVA 2:8. EtOH 96% proved superior to acetone/water for spray drying with polymers. The results were used to propose a general approach to developing spray-dried formulations of poorly soluble drugs.     

Solid-state amorphization of rebamipide and investigation on solubility and stability of the amorphous form

Solid-state amorphization of crystalline rebamipide (RBM) was realized by ball milling and spray drying. The amorphous content of samples milled for various time was quantified using X-ray powder diffraction. Crystalline RBM and three amorphous RBM obtained by milling and spray drying were characterized by morphological analysis, X-ray diffraction, thermal analysis and vibrational spectroscopy. The crystal structure of RBM was first determined by single-crystal X-ray diffraction. In addition, the solubility and dissolution rate of the RBM samples were investigated in different media. Results indicated that the solubility and the dissolution rates of spray-dried RBM-PVP in different media were highly improved compared with crystalline RBM. The physical stabilities of the three amorphous RBM were systematically investigated, and the stability orders under different storage temperatures and levels of relative humidity (RH) were both as follows: spray dried RBM?相似文献   

Effects of spray drying process parameters on the solubility behavior and physical stability of solid dispersions prepared using a laboratory-scale spray dryer

Purpose: The purpose of this study is to determine the process parameters of the laboratory-scale spray dryer affecting the solubility behavior and physical stability of solid dispersions.

Methods: Solid dispersions of the model drug (nilvadipine or nifedipine) and hypromellose (HPMC) (w/w: 1/1) were prepared using the laboratory-scale spray dryer. As process parameters, nitrogen flow rate, sample concentration and pump speed were investigated. The samples were characterized by dissolution tests, powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), scanning electron microscope (SEM), and nanoscale thermal analysis (Nano-TA). The physical stability was monitored after 7 months storage at 25°C.

Results: Solubility behavior and physical stability were improved by setting the low nitrogen flow rate and high sample concentration. DSC showed that the physical state depends on the spray drying conditions, whereas, every sample showed the similar morphology from SEM results. The difference of solubility behavior and physical stability were found to come from the microstructural phase separation of the spray dried particles using a novel analytical technique (Nano-TA).

Conclusions: This study demonstrated that nitrogen flow rate and sample concentration should be the critical parameters for the enhancements of the solubility and physical stability of solid dispersions.