How spray drying processing and solution composition can affect the mAbs stability in reconstituted solutions for subcutaneous injections. Part II: Exploring each protein stabilizer effect.

Despite extensive research in spray drying of biopharmaceuticals, identifying the optimal formulation composition and process conditions to minimize the various stresses a biopharmaceutical undergoes during this drying process. The current study extends previous research on investigating how spray drying processing and solution composition can affect the stability of monoclonal antibodies (mAbs) in reconstituted solutions for subcutaneous injections. The decoupling process stresses on a model mAb (mAb-A) compared to the effect of coupled spray-drying stresses revealed that excipients and protein concentration had a more pronounced effect on stabilizing mAb-A against shear and thermal/dehydration stresses than spray drying operating conditions. These results prompted the continuation of the study, with the aim to investigate in greater depth the effect of mAb-A concentration in the formulation designated to spray-drying and then the effect of type and the concentration of individual excipients (sugars, amino acids and surfactants). The outcomes of this investigation suggest that a general increase in the concentration of excipients, particularly surfactants, correlates with a reduction in aggregation and turbidity observed in the reconstituted spray-dried mAb-A powders. These results, contribute to the identification of a suitable composition for a spray-dried mAb-A powder that ensures robust stability of the protein in reconstituted solutions intended for subcutaneous injection. This valuable insight has important implications for advancing the development of pharmaceutical formulations with enhanced stability and efficacy.

How spray drying processing and solution composition can affect the mAbs stability in reconstituted solutions for subcutaneous injections. Part I: Contribution of processing stresses against composition.

Spray drying is increasingly being applied to process biopharmaceuticals, particularly monoclonal antibodies (mAbs). However, due to their protein nature, mAbs are susceptible to degradation when subjected to various stresses during a drying process. Despite extensive research in this domain, identifying the appropriate formulation composition and spray drying conditions remains a complex challenge, requiring further studies to enhance the understanding on how process and formulation parameters impact mAb stability in reconstituted solutions. This research aims to explore spray drying as technique for producing pharmaceutical mAbs-based powders intended for reconstitution and subcutaneous injection. In the initial phase of this study, using a model mAb (mAb-A), the influence of dissociated and coupled process stresses on protein stability after solution reconstitution was investigated. The findings revealed a detrimental interplay of mechanical, interfacial, and thermal/dehydration stresses on mAb-A stability, notably characterized by an increase in protein aggregation. Subsequently, in a second phase, the study delved into the impact of spray drying processing conditions, the level of excipients, and protein concentration on mAb-A aggregation in reconstituted solutions. The obtained results highlighted the critical role of formulation composition as a parameter deserving further study, specifically concerning the selection of type and concentration of stabilizers to be added in the liquid mAb-A solution to be dried.

Concordance of vacuum compression molding with spray drying in screening of amorphous solid dispersions of itraconazole.

Spray drying is a well-established method for screening spray dried dispersions (SDDs) but is material consuming, and the amorphous solid dispersions (ASDs) formed have low bulk density. Vacuum Compression Molding (VCM) is a potential method to avoid these limitations. This study focuses on VCM to screen ASDs containing itraconazole and L, M, or H polymer grades of hydroxypropyl methylcellulose acetate succinate (HPMCAS) and compares their morphology, amorphous stability, and dissolution performance with spray drying. Results indicate that VCM ASDs were comparable to SDDs. Both VCM ASDs and spray drying SDDs with HPMCAS-L and HPMCAS-M had improved dissolution profiles, while HPMCAS-H did not. Dynamic light scattering findings agreed with dissolution profiles, indicating that L and M grades produced monodisperse, smaller colloids, whereas H grade formed larger, polydisperse colloids. Capsules containing ASDs from VCM disintegrated and dissolved in the media; however, SDD capsules formed agglomerates and failed to disintegrate completely. Findings indicate that the VCM ASDs are comparable to SDDs in terms of dissolution performance and amorphous stability. VCM may be utilized in early ASD formulation development to select drug-polymer pairs for subsequent development.

Influence of pasteurization and spray drying on the fat digestion behavior of human milk fat analog emulsion: a simulated in vitro infant digestion study.

BACKGROUND: Human milk fat analog emulsion (HMFAE) is an emulsion that mimics the composition and structure of human milk (HM) fat globules. The application of HMFAE in infant formula requires a series of milk powder processing steps, such as pasteurization and spray drying. However, the effect of milk powder processing on fat digestion of HMFAE is still unclear. In this study, the influence of pasteurization and spray drying on the lipolysis behavior of HMFAE was studied and compared with HM using a simulated infant in vitro digestion model. RESULTS: Pasteurization and spray drying increased the flocculation and aggregation of lipid droplets in HMFAE during digestion. Spray drying destroyed the lipid droplet structure of HMFAE, and partial milk fat globule membrane-covered lipid droplets turned into protein-covered lipid droplets, which aggravated lipid-protein aggregation during gastric digestion and hindered fat digestion in the small intestine. The final lipolysis degree was in the order HM (64.55%) > HMFAE (63.41%) > pasteurized HMFAE (61.75%) > spray-dried HMFAE (60.57%). After complete gastrointestinal digestion, there were no significant differences in free fatty acid and sn-2 monoacylglycerol profile among the HMFAE, pasteurized HMFAE, and spray-dried HMFAE. CONCLUSION: Milk powder processing can reduce lipolysis by altering the lipid droplet structure of HMFAE and the degree of lipid droplet aggregation during digestion. © 2024 Society of Chemical Industry.

Solid self-microemulsifying drug delivery system (S-SMEDDS) prepared by spray drying to improve the oral bioavailability of cinnamaldehyde (CA).

The aim of this study was to prepare a solid self-microemulsifying drug delivery system (S-SMEDDS) of cinnamaldehyde (CA) by spray drying technique to improve the oral bioavailability of CA. The preparation of CA S-SMEDDS with maltodextrin as the solid carrier, a core-wall material mass ratio of 1:1, a solid content of 20% (w/v), an inlet air temperature of 150 °C, an injection speed of 5.2 mL/min, and an atomization pressure of 0.1 MPa was determined by using the encapsulation rate as the index of investigation. Differential scanning calorimetry (DSC) revealed the possibility of CA being encapsulated in S-SMEDDS in an amorphous form. The in-vitro release showed that the total amount of CA released by S-SMEDDS was approximately 1.3 times higher than that of the CA suspension. Pharmacokinetic results showed that the relative oral bioavailability of CA S-SMEDDS was also increased to 1.6-fold compared to CA suspension. Additionally, we explored the mechanism of CA uptake and transport of lipid-soluble drugs CA by S-SMEDDS in a Caco-2/HT29 cell co-culture system for the first time. The results showed that CA S-SMEDDS uptake on the co-culture model was mainly an energy-dependent endocytosis mechanism, including lattice protein-mediated endocytosis and vesicle-mediated endocytosis. Transport experiments showed that CA S-SMEDDS significantly increased the permeability of CA in this model. These findings suggested that CA S-SMEDDS is an effective oral solid dosage form for increasing the oral bioavailability of lipid-soluble drug CA.

Understanding the mechanisms of ß-glucan regulating the in vitro starch digestibility of highland barley starch under spray drying: Structure and physicochemical properties.

This study investigated the effects of ß-glucan (0-6%) on the physicochemical properties, structure, and in vitro digestibility of highland barley starch (HBS) under spray drying (SD). SD significantly enhanced the inhibitory effect of 6% ß-glucan on the in vitro digestibility and glucose diffusion of HBS. After SD, the addition of ß-glucan at 4% and 6% concentration significantly increased the pasting temperatures of starch while decreased the rheological properties. Thermal properties demonstrated that ß-glucan improved the thermal stability and residue content of HBS at 600°C, lowered its maximum loss rate, and maintained its thermal stability after SD. Structural properties showed that ß-glucan affected greatly on amorphous regions of HBS after SD. Additionally, ß-glucan dispersed more evenly in the starch system and experienced hydrogen bonding with starch after SD. This study presents a novel approach to enhancing the inhibitory effect of ß-glucan on starch digestion.

The interplay between trehalose and dextran as spray drying precursors for cationic liposomes.

Successful oral delivery of liposomes requires formulations designed to withstand harsh gastrointestinal conditions, e.g., by converting to solid-state followed by loading into gastro-resistant delivery devices. The hypothesis was that the use of dextran-trehalose mixtures for spray drying would improve the rehydration kinetics of dried liposomes. The objectives were to determine the protective capacity of trehalose-dextran dehydration precursors and to increase the concentration of liposomes in the dry formulation volume. The study successfully demonstrated that 8.5% dextran combined with 76.5% trehalose protected CAF®04 liposomes during drying, with the liposome content maintained at 15% of the dry powder. Accordingly, the rehydration kinetics were slightly improved in formulations containing up to 8.5% dextran in the dry powder volume. Additionally, a 2.4-fold increase in lipid concentration (3 mM vs 7.245 mM) was achieved for spray dried CAF®04 liposomes. Ultimately, this study demonstrates the significance of trehalose as a primary carrier during spray drying of CAF®04 liposomes and highlights the advantage of incorporating small amounts of dextran to tune rehydration kinetics of spray-dried liposomes.

Physicochemical properties of amorphous granular starch (AGS) prepared by non-thermal gelatinization by high hydrostatic pressure (HHP) and spray drying.

Corn starch was gelatinized by high hydrostatic pressure (HHP) and spray drying to make amorphous granular starch (AGS), and their physicochemical properties were compared with the conventionally prepared (heat-gelatinized and spray dried) AGS to devise a novel AGS preparation methodology. Pressure-induced (PAGS) and heat-induced AGS (HAGS) maintained their granular shape but lost their birefringence indicating that both methods could prepare AGS. DSC (differential scanning calorimeter) and XRD (X-ray diffraction) analysis confirmed the complete loss of amylopectin double helices and crystallinity of both PAGS and HAGS. However, their swelling power, solubility, RVA pasting properties, acid/shear stability, gel forming ability and textural properties were completely different. PAGS exhibited constrained swelling, suppressed amylose leaching, and reduced viscosity. Notably, HAGS formed a gel without heating, whereas PAGS yielded a viscous paste with water-soluble attributes. Even after reheating, PAGS maintained its granular structure with comparably less swelling and weaker gel strength than HAGS. Consequently, newly developed PAGS exhibited distinctive characteristics compared to the conventional HAGS, such as lower solubility and swelling power, viscosity, textural properties, and high acid and shear stabilities, rendering it a viable option for various applications within the food industry.

Effect of nanobubbles on powder morphology in the spray drying process.

This study investigated the influence of gas-injected nanobubbles on the morphology of particles during spray drying under various experimental conditions. The nanoparticle tracking system was used to measure the generation, size, and concentration of nanobubbles. Experiments were conducted at different temperatures (160°C-260°C) and feed rates (0.2-0.26 g/s) to examine the effect of nanobubbles on spray drying and present diverse results. The deionized (DI) water with generated nanobubbles had a particle concentration of 1.8 × 108 particles/mL and a mean particle size of 242.6 nm, which was ∼3.31 × 107 particles/mL higher untreated DI water. The maltodextrin solution containing nanobubbles also showed a significant increase in particle generation, with a concentration of 1.62 × 109 particles/mL. The viscosity of the maltodextrin solution containing nanobubbles decreased by ∼18%, from 9.3 mPa·s to 7.5 mPa·s. Overall, the size of the generated particles was similar regardless of nanobubble treatment, but there was a tendency for particle size to increase under specific temperature (260°C) and feed flow rate (0.32 g/s) conditions. Furthermore, it was observed that the Hausner ratio significantly varied with increasing temperature and feed flow rate, and these results were explained through scanning electron microscopy images. These findings confirm that the gas nanobubbles mixed in the feed can exert diverse effects on the spray drying system and powder characteristics depending on the operating conditions. This study suggests that nanobubbles can contribute to a more efficient process in spray drying and can influence the morphological characteristics of particles depending on the spray drying conditions.

Carriers based on dairy by-products and dehumidified-air spray drying as a novel multiple approach towards improved retention of phenolics in powders: sour cherry juice concentrate case study.

BACKGROUND: Sour cherry juice concentrate powder can serve as a modern, easy-to-handle, phenolics-rich merchandise; however, its transformation into powdered form requires the addition of carriers. In line with the latest trends in food technology, this study valorizes the use of dairy by-products (whey protein concentrate, whey, buttermilk, and mixes with maltodextrin) as carriers. A new multiple approach for higher drying yield, phenolics retention (phenolic acids, flavonols and anthocyanins) and antioxidant capacity of powders were tested as an effect of simultaneous decrease of drying temperature due to the drying air dehumidification and lower carrier content. RESULTS: Dairy-based carriers were effective for spray drying of sour cherry-juice concentrate. The drying yield was increased and retention of phenolics was higher when compared with maltodextrin. The application of dehumidified air, which enabled the drying temperature to be reduced, affected drying yield positively, and also affected particle morphology and retention of phenolics (the phenolic content was approximately 30% higher than with spray drying). CONCLUSIONS: The study proved that it is possible to apply dairy-based by-products to produce sour cherry juice concentrate powders profitably, lowering the spray-drying temperature and changing the carrier content. Dehumidified air spray drying can be recommended for the production of fruit juice concentrate powders with improved physicochemical properties. © 2023 Society of Chemical Industry.

Rapid screening of ternary amorphous formulations by a spray drying robot.

Spray drying is commonly used for producing amorphous solid dispersions to improve drug solubility. The development of such formulations typically relies on comprehensive excipient and composition screening, which requires the preparation of many spray-dried powder samples. This is both labour-intensive and time-consuming when carried out manually. In the present work, the formulation screening task was automated by coupling a laboratory spray dryer operated in a semi-continuous mode with custom-made add-ons, allowing for rapid, computer-controlled production of formulation samples with systematically varying composition. The practical use of the spray drying robot in formulation development was demonstrated on a case study of poorly water-soluble model drugs simvastatin and ezetimibe. Six different polymers and several drug:polymer ratios were screened for the enhancement of dissolution properties. From a pool of 28 spray-dried samples, ternary compositions containing Eudragit L100-55 were identified as the most suitable ones for further processing and characterisation. The ability to populate the formulation design space rapidly and automatically made it possible to construct maps of physico-chemical properties such as glass transition temperature or dissolution rate. The spray drying robot thus enables the acceleration of early formulation development and a deeper understanding of composition-property relationships for multi-component spray dried powders.

[Application prospect of reaction engineering approach in studying drying behavior of single droplet during spray drying of traditional Chinese medicine].

Spray drying technology is one of the most commonly used unit operations in the production of traditional Chinese medicine(TCM) preparations, offering advantages such as short drying time and uniform product quality. However, due to the properties of TCM extracts, such as high viscosity, strong hygroscopicity, and poor flowability, there is limited scope to solve the problems of wall adhesion and clumping in spray drying from the macroscopic perspective of pharmaceutical production. Therefore, it has become a trend to study and optimize the spray drying process from the microscopic point of view by investigating single droplet evaporation behavior. Based on the reaction engineering approach(REA), the single droplet drying system, as a novel method for studying droplets, collects parameter data on individual TCM droplets during the drying process and uses the REA to process the data and establish predictive models. This approach is crucial for understanding the mechanism of TCM spray drying. This paper summarized and analyzed the cha-racteristics of various single droplet systems, the application of REA in single droplet drying systems, and its significance in optimizing the process, predicting drying states, and shortening the development cycle in the field of TCM spray drying, and looked ahead to the prospects of this method, including the introduction of new parameters and imaging techniques, aiming to provide a reference for further research in the field of TCM spray drying.

Study on Improving the Performance of Traditional Medicine Extracts with High Drug Loading Based on Co-spray Drying Technology.

The purpose of this study is to develop modified particles with different structures to improve the flowability and compactibility of Liuwei Dihuang (LWDH) powder using co-spray drying technology, and to investigate the preparation mechanism of modified particles and their modified direct compaction (DC) properties. Moreover, tablets with high drug loading contents were also prepared. Particles were designed using polyvinylpyrrolidone (PVP K30) and hydroxypropyl methylcellulose (HPMC E3) as shell materials, and sodium bicarbonate (NaHCO3) and ammonium bicarbonate (NH4HCO3) as pore-forming agents. The porous particles (Ps), core-shell particles (CPs), and porous core-shell particles (PCPs) were prepared by co-spray drying technology. The key DC properties and texture properties of all the particles were measured and compared. The properties of co-spray drying liquid were also determined and analyzed. According to the results, Ps showed the least improvement in DC properties, followed by CPs, and PCPs showed a significant improvement. The modifier, because of its low surface tension, was wrapped in the outer layer to form a shell, and the pore-forming agent was thermally decomposed to produce pores, forming core-shell, porous, and porous core-shell composite structures. The smooth surface of the shell structure enhances fluidity, while the porous structure allows for greater compaction space, thereby improving DC properties during the compaction process.

Supersaturable Solid Self-microemulsifying Delivery Systems of Astaxanthin via Spray Drying: Effects of Polymers and Solid Carriers.

This study aimed to develop the solid astaxanthin-encapsulated self-microemulsifying delivery system (S-AST SMEDS) spray-dried particles and investigate the effect of materials in formulations on product characteristics. The optimized liquid AST SMEDS incorporated with a polymeric precipitation inhibitor (PI) was solidified with a solid carrier by spray drying. Physicochemical properties of S-AST SMEDS spray-dried powders including morphology, particle size and distribution, flowability, solid-state characters, moisture content, yield, loading capacity of AST, and reconstitution properties were examined. Polymeric PIs seemed to have an impact on particles' size, surface smoothness, and flowability while solid carriers had an effect on the particles' moisture content and droplet size of microemulsions obtained after reconstitution. The amount of AST encapsulated in S-SMEDS powder was influenced by both polymer and solid carriers. Dissolution and short-term stability of S-AST SMEDS were also studied. Our developed spray-dried solid SMEDS particles helped enhance AST dissolution rate.

Application of spray drying, spray chilling and the combination of both methods to produce tucumã oil microparticles: characterization, stability, and ß-carotene bioaccessibility.

The aim of this work was to produce tucumã oil (PO) microparticles using different encapsulation methods, and to evaluate their properties, storage stability and bioaccessibility of the encapsulated ß-carotene. Gum Arabic was used as carrier for spray drying (SD), while vegetable fat was the wall material for spray chilling (SC) and the combination of the methods (SDC). Powders were yellow (hue angle around 80°) and presented particles with small mean diameters (1.57-2.30 µm). PO and the microparticles possess high ß-carotene contents (∼0.35-22 mg/g). However, some carotenoid loss was observed in the particles after encapsulation by SD and SDC (around 20%). After 90 days of storage, SDC particles presented the lowest degradation of total carotenoids (∼5%), while SD samples showed the highest loss (∼21%). Yet, the latter had the lowest contents of conjugated dienes (4.1-5.3 µmol/g) among treatments. At the end of simulated digestion, PO and the microparticles provided low ß-carotene bioaccessibility (<10%), and only SC increased this parameter compared to the pure oil. In conclusion, carotenoid-rich microparticles with attractive color were obtained through microencapsulation of PO by SD, SC and SDC, revealing their potential as natural additives for the development of food products with improved nutritional properties. The SC method stood out for providing microparticles with high carotenoid content and retention, high oxidative stability, and improved ß-carotene bioaccessibility.

Use of microencapsulated starter cultures by spray drying in coffee under self-induced anaerobiosis fermentation (SIAF).

Using starter culture in liquid form is not economically viable in the coffee fermentation process. This work aimed to compare the fermentative performances of fresh and microencapsulated yeasts in coffee under self-induced anaerobic fermentation (SIAF). The inoculum permanence was monitored, and sugars, alcohols, acids, and volatile compounds were analyzed by chromatography. In addition, sensory analysis was performed on roasted beans. After 180 h of fermentation in the natural process, microencapsulated Torulaspora delbrueckii (MT) (7.97 × 107 cells/g) showed a higher population thanfresh Torulaspora delbrueckii (FT) (1.76 × 107 cells/g). The same acids and volatile compounds were detected in coffees with fresh and microencapsulated yeast. However, the yeast state influenced the concentration of the compounds. In pulped coffee, the coffee inoculated withmicroencapsulated Saccharomyces cerevisiae (MS) obtained the highest concentration of alcohols, esters, pyrazines, and others compared with fresh Saccharomyces cerevisiae (FS), with an increase of up to 47%. Furthermore, the coffee inoculated with MT obtained the highest concentration in almost all chemical classes in both processes compared with FT. These differences ranged up to 55%. Regarding sensory analysis, coffees inoculated with MS showed dominant notes of fruity, caramel, and nuts in the natural process. Otherwise, in pulped process, coffees inoculated with MT showed caramel, honey, and nuts. Therefore, the microencapsulated yeasts were metabolically active and may be considered with commercial potential. Considering the parameters analyzed, the most suitable yeast for natural and pulped processing would be MS and MT, respectively.

Rice bran protein increases the retention of anthocyanins by acting as an encapsulating agent in the spray drying of grape juice.

Rice bran protein concentrate (RPC), an industrial by-product, may emerge as a green alternative for substituting animal proteins in microencapsulating compounds of interest. This study applied RPC, combined with maltodextrin (MD) as carrier agents, in the spray drying of grape juice, a product rich in these bioactive compounds, seeking to protect anthocyanins from degradation. The effects of carrier agent concentration [C: 0.75, 1.00, and 1.25 g of carrier agents (CA)/g of soluble solids of the juice (SS)] and RPC:CA ratio (P: 0%, as a control sample, 5%, 10%, 15%, and 20%) on anthocyanin retention and powder properties were evaluated. At 1.00 g CA/g SS, the internal and total retentions of anthocyanins improved by 2.4 and 3.2 times, respectively, when the RPC:CA ratio increased from 0% to 20%. The protein also exhibited excellent surface activity on the grape juice and positively influenced the physicochemical properties of the microparticles. There was a reduction in stickiness, degree of caking, and hygroscopicity, in addition to an increased antioxidant capacity when protein was used in combination with MD, especially at 1.00 and 1.25 g CA/g SS. Therefore, this study demonstrated that RPC could enhance the protection of anthocyanins during the spray drying of grape juice.

Co-encapsulation of Paprika and Cinnamon Oleoresins by Spray Drying in a Mayonnaise Model: Bioaccessibility of Carotenoids Using in vitro Digestion.

This study aimed to investigate the digestibility and bioaccessibility of spray-dried microparticles co-encapsulating paprika and cinnamon oleoresins using simulated gastrointestinal conditions. It focused on exploring the potential of these co-encapsulated active compounds, which possess diverse technological and functional properties, particularly within a food matrix, in order to enhance their bioavailability. Mayonnaise was selected as the food matrix for its ability to promote the diffusion of carotenoids, as most hydrophobic compounds are better absorbed in the intestine when accompanied by digestible lipids. Model spice mayonnaise, containing 0.5 wt% paprika and cinnamon microparticles content, was formulated in compliance with Brazilian regulations for spices, seasonings, and sauce formulations. Droplet size distribution, optical microscopy and fluorescence microscopy analyses were conducted on the microparticles, model spice mayonnaise, and standard mayonnaise both before and after in vitro gastric and intestinal digestion. Following digestion, all samples demonstrated droplet aggregation and coalescence. Remarkably, dispersed particles (37.40 ± 2.58%) and model spice mayonnaise (17.76 ± 0.07%) showed the highest release rate of free fatty acids (FFAs), indicating efficient lipid digestion. The study found that using mayonnaise as a delivery system significantly increased bioaccessibility (22.7%). This suggests that particles in an aqueous medium have low solubility, while the high lipid composition of mayonnaise facilitates the delivery of active compounds from carotenoids present in paprika and cinnamon oleoresin after digestion.

Microencapsulation by spray-drying and freeze-drying of extract of phenolic compounds obtained from ciriguela peel.

Microcapsules of ciriguela peel extracts obtained by ultrasound-assisted extraction were prepared by spray drying, whose results were compared with those of freeze-drying as a control. The effects of spray-drying air temperature, feed flow rate and ratio of encapsulating agents (maltodextrin and arabic gum) were studied. Encapsulation efficiency, moisture content, total phenolic compounds (TPC), water activity, hygroscopicity, solubility, colorimetric parameters, phenolic profile by HPLC/DAD, simulated gastrointestinal digestion and morphology of spray-dried and freeze-dried microcapsules were evaluated, as well as their stability of TPC during 90 days storage at 7 and 25 °C. Spray-dried extract showed higher encapsulation efficiency (98.83%) and TPC (476.82 mg GAE g-1) than freeze-dried extract. The most abundant compounds in the liquid extract of ciriguela peel flour were rutin, epicatechin gallate, chlorogenic acid and quercetin. Rutin and myricetin were the major flavonoids in the spray-dried extract, while quercetin and kaempferol were in the freeze-dried one. The simulated gastrointestinal digestion test of microencapsulated extracts revealed the highest TPC contents after the gastric phase and the lowest one after the intestinal one. Rutin was the most abundant compound after the digestion of both spray-dried (68.74 µg g-1) and freeze-dried (93.98 µg g-1) extracts. Spray-dried microcapsules were of spherical shape, freeze-dried products of irregular structures. Spray-dried microcapsules had higher phenolic compounds contents after 90 days of storage at 7 °C compared to those stored at 25 °C, while the lyophilized ones showed no significant difference between the two storage temperatures. The ciriguela agro-industrial residue can be considered an interesting alternative source of phenolic compounds that could be used, in the form of bioactive compounds-rich powders, as an ingredient in pharmaceutical, cosmetic and food industries.

In Situ Cocrystallization via Spray Drying with Polymer as a Strategy to Prevent Cocrystal Dissociation.

The aim of the present study was to investigate how different polymers affect the dissociation of cocrystals prepared by co-spray-drying active pharmaceutical ingredient (API), coformer, and polymer. Diclofenac acid-l-proline cocrystal (DPCC) was selected in this study as a model cocrystal due to its previously reported poor physical stability in a high-humidity environment. Polymers investigated include polyvinylpyrrolidone (PVP), poly(1-vinylpyrrolidone-co-vinyl acetate) (PVPVA), hydroxypropyl methyl cellulose, hydroxypropylmethylcellulose acetate succinate, ethyl cellulose, and Eudragit L-100. Terahertz Raman spectroscopy (THz Raman) and powder X-ray diffraction (PXRD) were used to monitor the cocrystal dissociation rate in a high-humidity environment. A Raman probe was used in situ to monitor the extent of the dissociation of DPCC and DPCC in crystalline solid dispersions (CSDs) with polymer when exposed to pH 6.8 phosphate buffer and water. The solubility of DPCC and solid dispersions of DPCC in pH 6.8 phosphate buffer and water was also measured. The dissociation of DPCC was water-mediated, and more than 60% of DPCC dissociated in 18 h at 40 °C and 95% RH. Interestingly, the physical stability of the cocrystal was effectively improved by producing CSDs with polymers. The inclusion of just 1 wt % polymer in a CSD with DPCC protected the cocrystal from dissociation over 18 h under the same conditions. Furthermore, the CSD with PVPVA was still partially stable, and the CSD with PVP was stable (undissociated) after 7 days. The superior stability of DPCC in CSDs with PVP and PVPVA was also demonstrated when systems were exposed to water or pH 6.8 phosphate buffer and resulted in higher dynamic solubility of the CSDs compared to DPCC alone. The improvement in physical stability of the cocrystal in CSDs was thought to be due to an efficient mixing between polymer and cocrystal at the molecular level provided by spray drying and in situ gelling of polymer. It is hypothesized that polymer chains could undergo gelling in situ and form a physical barrier, preventing cocrystal interaction with water, which contributes to slowing down the water-mediated dissociation.