Pharmaceutics

Research

12 pages, 923 KiB

Open AccessFeature PaperArticle

Preparation of Co-Amorphous Systems by Freeze-Drying

by Melvin Wostry, Hanna Plappert and Holger Grohganz

Pharmaceutics 2020, 12(10), 941; https://doi.org/10.3390/pharmaceutics12100941 - 30 Sep 2020

Cited by 17 | Viewed by 3518

Freeze-drying was evaluated as a production technique for co-amorphous systems of a poorly water-soluble drug. Naproxen was freeze-dried together with arginine and lysine as co-former. To increase the solubility of naproxen in the starting solution, the applicability of five surfactants was investigated, namely [...] Read more.

Freeze-drying was evaluated as a production technique for co-amorphous systems of a poorly water-soluble drug. Naproxen was freeze-dried together with arginine and lysine as co-former. To increase the solubility of naproxen in the starting solution, the applicability of five surfactants was investigated, namely sodium dodecyl sulfate, pluronic F-127, polyoxyethylene (40) stearate, tween 20 and TPGS 1000. The influence of the surfactant type, surfactant concentration and total solid content to be freeze-dried on the solid state of the sample was investigated. X-ray powder diffraction and differential scanning calorimetry showed that the majority of systems formed co-amorphous one-phase systems. However, at higher surfactant concentrations, and depending on the surfactant type, surfactant reflections were observed in the XRPD analysis upon production. Crystallization of both naproxen and amino acid occurred from some combinations under storage. In conclusion, freeze-drying was shown to be a feasible technique for the production of a selection of co-amorphous drug–amino acid formulations. Full article

(This article belongs to the Special Issue Pharmaceutical Freeze Drying and Spray Drying)

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15 pages, 2332 KiB

Open AccessArticle

Selection of Cryoprotectant in Lyophilization of Progesterone-Loaded Stearic Acid Solid Lipid Nanoparticles

by Timothy M. Amis, Jwala Renukuntla, Pradeep Kumar Bolla and Bradley A. Clark

Pharmaceutics 2020, 12(9), 892; https://doi.org/10.3390/pharmaceutics12090892 - 19 Sep 2020

Cited by 40 | Viewed by 5545

Abstract

Cryoprotectants are often required in lyophilization to reduce or eliminate agglomeration of solute or suspended materials. The aim of this study was to select a cryoprotecting agent and optimize its concentration in a solid lipid nanoparticle formulation. Progesterone-loaded stearic acid solid lipid nanoparticles [...] Read more.

Cryoprotectants are often required in lyophilization to reduce or eliminate agglomeration of solute or suspended materials. The aim of this study was to select a cryoprotecting agent and optimize its concentration in a solid lipid nanoparticle formulation. Progesterone-loaded stearic acid solid lipid nanoparticles (SA-P SLNs) were prepared by hot homogenization with high speed mixing and sonication. The stearic acid content was 4.6% w/w and progesterone was 0.46% w/w of the initial formulation. Multiple surfactants were evaluated, and a lecithin and sodium taurocholate system was chosen. Three concentrations of surfactant were then evaluated, and a concentration of 2% w/w was chosen based on particle size, polydispersity, and zeta potential. Agglomeration of SA-P SLNs after lyophilization was observed as measured by increased particle size. Dextran, glycine, mannitol, polyvinylpyrrolidone (PVP), sorbitol, and trehalose were evaluated as cryoprotectants by both an initial freeze–thaw analysis and after lyophilization. Once selected as the cryoprotectant, trehalose was evaluated at 5%, 10%, 15%, and 20% for optimal concentration, with 20% trehalose being finally selected as the level of choice. Evaluation by DSC confirmed intimate interaction between stearic acid and progesterone in the SA-P SLNs, and polarized light microscopy shows successful lyophilization of the trehalose/SA-P SLN. A short term 28-day stability study suggests the need for refrigeration of the final lyophilized SA-P SLNs in moisture vapor impermeable packaging. Full article

(This article belongs to the Special Issue Pharmaceutical Freeze Drying and Spray Drying)

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17 pages, 14605 KiB

Open AccessArticle

4D Micro-Computed X-ray Tomography as a Tool to Determine Critical Process and Product Information of Spin Freeze-Dried Unit Doses

by Brecht Vanbillemont, Joris Lammens, Wannes Goethals, Chris Vervaet, Matthieu N. Boone and Thomas De Beer

Pharmaceutics 2020, 12(5), 430; https://doi.org/10.3390/pharmaceutics12050430 - 7 May 2020

Cited by 13 | Viewed by 3333

Abstract

Maintaining chemical and physical stability of the product during freeze-drying is important but challenging. In addition, freeze-drying is typically associated with long process times. Therefore, mechanistic models have been developed to maximize drying efficiency without altering the chemical or physical stability of the [...] Read more.

Maintaining chemical and physical stability of the product during freeze-drying is important but challenging. In addition, freeze-drying is typically associated with long process times. Therefore, mechanistic models have been developed to maximize drying efficiency without altering the chemical or physical stability of the product. Dried product mass transfer resistance (

R_{p}

) is a critical input for these mechanistic models. Currently available techniques to determine

R_{p}

only provide an estimation of the mean

R_{p}

and do not allow measuring and determining essential local (i.e., intra-vial)

R_{p}

differences. In this study, we present an analytical method, based on four-dimensional micro-computed tomography (4D-

μ

CT), which enables the possibility to determine intra-vial

R_{p}

differences. Subsequently, these obtained

R_{p}

values are used in a mechanistic model to predict the drying time distribution of a spin-frozen vial. Finally, this predicted primary drying time distribution is experimentally verified via thermal imaging during drying. It was further found during this study that 4D-

μ

CT uniquely allows measuring and determining other essential freeze-drying process parameters such as the moving direction(s) of the sublimation front and frozen product layer thickness, which allows gaining accurate process knowledge. To conclude, the study reveals that the variation in the end of primary drying time of a single vial could be predicted accurately using 4D-

μ

CT as similar results were found during the verification using thermal imaging. Full article

(This article belongs to the Special Issue Pharmaceutical Freeze Drying and Spray Drying)

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16 pages, 3054 KiB

Open AccessArticle

The Influence of Moisture Content and Temperature on the Long-Term Storage Stability of Freeze-Dried High Concentration Immunoglobulin G (IgG)

by Arnold Duralliu, Paul Matejtschuk, Paul Stickings, Laura Hassall, Robert Tierney and Daryl R. Williams

Pharmaceutics 2020, 12(4), 303; https://doi.org/10.3390/pharmaceutics12040303 - 27 Mar 2020

Cited by 26 | Viewed by 4813

Abstract

High protein concentration products for targeted therapeutic use are often freeze-dried to enhance stability. The long-term storage stability of freeze-dried (FD) plasma-derived Immunoglobulin G (IgG) from moderate to high concentrations (10–200 mg/mL) was assessed. Monomer content, binding activity and reconstitution times were evaluated [...] Read more.

High protein concentration products for targeted therapeutic use are often freeze-dried to enhance stability. The long-term storage stability of freeze-dried (FD) plasma-derived Immunoglobulin G (IgG) from moderate to high concentrations (10–200 mg/mL) was assessed. Monomer content, binding activity and reconstitution times were evaluated over a 12-month period under accelerated and real-term storage conditions. In the first case study it was shown that FD IgG from 10 to 200 mg/mL had minimal monomer/activity losses at up to ambient temperature after 12 months of storage. However, at 45 °C the sucrose-to-protein ratio played a significant impact on IgG stability above 50 mg/mL. All IgG concentrations witnessed moisture ingress over a 12-month period. The impact of moisture ingress from environmental exposure (between 0.1% and 5% w/w moisture) for IgG 50 mg/mL was assessed, being generated by exposing low moisture batches to an atmospheric environment for fixed time periods. Results showed that at −20 °C and 20 °C there was no significant difference in terms of monomer or antigen-binding activity losses over 6 months. However, at 45 °C, there were losses in monomer content, seemingly worse for higher moisture content samples although model binding activity indicated no losses. Finally, the difference between a low moisture product (0.1–1% w/w) and a moderately high moisture (3% w/w) product generated by alternative freeze-drying cycles, both stoppered under low oxygen headspace conditions, was evaluated. Results showed that at −20 °C and 20 °C there was no difference in terms of binding activity or monomer content. However, at 45 °C, the low moisture samples had greater monomer and binding activity losses than samples from the highest moisture cycle batch, indicating that over-drying can be an issue. Full article

(This article belongs to the Special Issue Pharmaceutical Freeze Drying and Spray Drying)

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21 pages, 9470 KiB

Open AccessArticle

Model-Based Optimisation and Control Strategy for the Primary Drying Phase of a Lyophilisation Process

by Brecht Vanbillemont, Niels Nicolaï, Laurens Leys and Thomas De Beer

Pharmaceutics 2020, 12(2), 181; https://doi.org/10.3390/pharmaceutics12020181 - 20 Feb 2020

Cited by 17 | Viewed by 5002

Abstract

The standard operation of a batch freeze-dryer is protocol driven. All freeze-drying phases (i.e., freezing, primary and secondary drying) are programmed sequentially at fixed time points and within each phase critical process parameters (CPPs) are typically kept constant or linearly interpolated between two [...] Read more.

The standard operation of a batch freeze-dryer is protocol driven. All freeze-drying phases (i.e., freezing, primary and secondary drying) are programmed sequentially at fixed time points and within each phase critical process parameters (CPPs) are typically kept constant or linearly interpolated between two setpoints. This way of operating batch freeze-dryers is shown to be time consuming and inefficient. A model-based optimisation and real-time control strategy that includes model output uncertainty could help in accelerating the primary drying phase while controlling the risk of failure of the critical quality attributes (CQAs). In each iteration of the real-time control strategy, a design space is computed to select an optimal set of CPPs. The aim of the control strategy is to avoid product structure loss, which occurs when the sublimation interface temperature (

T_{i}

) exceeds the the collapse temperature (

T_{c}

) common during unexpected disturbances, while preventing the choked flow conditions leading to a loss of pressure control. The proposed methodology was experimentally verified when the chamber pressure and shelf fluid system were intentionally subjected to moderate process disturbances. Moreover, the end of the primary drying phase was predicted using both uncertainty analysis and a comparative pressure measurement technique. Both the prediction of

T_{i}

and end of primary drying were in agreement with the experimental data. Hence, it was confirmed that the proposed real-time control strategy is capable of mitigating the effect of moderate disturbances during batch freeze-drying. Full article

(This article belongs to the Special Issue Pharmaceutical Freeze Drying and Spray Drying)

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10 pages, 5562 KiB

Open AccessArticle

Energy Transfer in Vials Nested in a Rack System During Lyophilization

by Sarah Daller, Wolfgang Friess and Rudolf Schroeder

Pharmaceutics 2020, 12(1), 61; https://doi.org/10.3390/pharmaceutics12010061 - 11 Jan 2020

Cited by 11 | Viewed by 4640

Abstract

Small batch sizes are a consequence of more personalized medicine and reflect a trend in the biopharmaceutical industry. Freeze drying of vials nested in a rack system is a tool used in new flexible pilot scale processing lines. Understanding of heat transfer mechanisms [...] Read more.

Small batch sizes are a consequence of more personalized medicine and reflect a trend in the biopharmaceutical industry. Freeze drying of vials nested in a rack system is a tool used in new flexible pilot scale processing lines. Understanding of heat transfer mechanisms in the rack loaded with vials not in direct contact with each other is necessary to ensure high quality. Lyophilization in the rack vial system enables a homogeneous drying with a reduced edge-vial-effect and shielding against radiation from surrounding components, e.g., the chamber wall. Due to the separation effect of the rack, direct shelf contact contributes approx. 40% to the overall energy transfer to the product during primary drying. Hence overall the rack is a flexible, robust tool for small batch production, which ensures a controlled heat transfer resulting in a uniform product. Full article

(This article belongs to the Special Issue Pharmaceutical Freeze Drying and Spray Drying)

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15 pages, 3163 KiB

Open AccessArticle

Spray Dried Formulations for Inhalation—Meaningful Characterisation of Powder Properties

by Angelika Jüptner and Regina Scherließ

Pharmaceutics 2020, 12(1), 14; https://doi.org/10.3390/pharmaceutics12010014 - 21 Dec 2019

Cited by 22 | Viewed by 4563

Abstract

Spray drying as a particle engineering technique is of increasing interest in the field of inhalation and is already being utilised e.g., for the PulmoSphere^TM products. As spray dried particles tend to agglomerate and are mechanically instable, low dose filling processes can [...] Read more.

Spray drying as a particle engineering technique is of increasing interest in the field of inhalation and is already being utilised e.g., for the PulmoSphere^TM products. As spray dried particles tend to agglomerate and are mechanically instable, low dose filling processes can be difficult. This study correlates powder flowability tests of spray dried formulations with filling processes with drum and dosator systems. Four pulmonary and four nasal powders with different characteristics in terms of shape, composition, and surface polarity were prepared and characterised for powder flowability according to Ph. Eur. and by powder rheometry. All formulations were filled with a manual drum TT and a dosator system. The classical flowability tests according to the Ph. Eur. showed a bad flow behaviour for hydrophilic pulmonary powders (x₅₀ ~ 3 µm), whereas hydrophobic pulmonary particles and nasal particles (x₅₀ ~ 25 µm) showed a better flowing behaviour. Powder rheometry supports this finding but can better differentiate flow behaviours. Full article

(This article belongs to the Special Issue Pharmaceutical Freeze Drying and Spray Drying)

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21 pages, 5968 KiB

Open AccessArticle

Microwave-Assisted Freeze-Drying of Monoclonal Antibodies: Product Quality Aspects and Storage Stability

by Julian Hendryk Gitter, Raimund Geidobler, Ingo Presser and Gerhard Winter

Pharmaceutics 2019, 11(12), 674; https://doi.org/10.3390/pharmaceutics11120674 - 12 Dec 2019

Cited by 23 | Viewed by 4314

Abstract

In order to overcome the downside of long conventional freeze-drying (CFD) process times for monoclonal antibody formulations, microwave-assisted freeze-drying (MFD) was introduced. Recently, the general applicability and potential shortening of drying times were shown. However, little is known about the storage stability of [...] Read more.

In order to overcome the downside of long conventional freeze-drying (CFD) process times for monoclonal antibody formulations, microwave-assisted freeze-drying (MFD) was introduced. Recently, the general applicability and potential shortening of drying times were shown. However, little is known about the storage stability of MFD products compared to CFD references. Additionally, batch homogeneity issues were seen within MFD in the past. In this study, we examined four different formulations of two different monoclonal antibodies using three different glass-forming excipients: sucrose, trehalose, and arginine phosphate. These formulations were freeze-dried with two different drying protocols (CFD and MFD), stored for 24 weeks, and analyzed for solid-state and protein-related quality attributes. Moreover, a new microwave generator setup was investigated for its potential to improve batch homogeneity. In all investigated formulations, comparable stability profiles were found, although the classical magnetron generator led to inferior batch homogeneity with respect to residual moisture distribution. In contrast, the new MFD setup indicated the potential to approximate batch homogeneity to the level of CFD. However, for future applications, there is an unabated need for new machine designs to comply with pharmaceutical manufacturing requirements. Full article

(This article belongs to the Special Issue Pharmaceutical Freeze Drying and Spray Drying)

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21 pages, 2763 KiB

Open AccessArticle

A Novel Rheological Method to Assess Drug-Polymer Interactions Regarding Miscibility and Crystallization of Drug in Amorphous Solid Dispersions for Oral Drug Delivery

by Georgia Tsakiridou, Christos Reppas, Martin Kuentz and Lida Kalantzi

Pharmaceutics 2019, 11(12), 625; https://doi.org/10.3390/pharmaceutics11120625 - 22 Nov 2019

Cited by 9 | Viewed by 4161

Abstract

Solid dispersions provide a key technology to formulate poorly water-soluble drugs, and a main task of early development is appropriate selection of polymer. This study investigates the use of a novel rheology-based approach to evaluate miscibility and interactions of drugs with polymers regarding [...] Read more.

Solid dispersions provide a key technology to formulate poorly water-soluble drugs, and a main task of early development is appropriate selection of polymer. This study investigates the use of a novel rheology-based approach to evaluate miscibility and interactions of drugs with polymers regarding amorphous solid drug dispersions for oral administration. Tacrolimus was used as model drug and hydroxypropyl cellulose, ethylcellulose, Soluplus^®, polyethyleneglycol 6000, Poloxamer-188 (Koliphor-188), and Eudragit^® S100 were used as excipients. Solvent-based evaporation methods were used to prepare binary solid dispersions of drug and polymer. Data of the dilute solution viscosimetry were compared with in silico calculations of the Hansen solubility parameter (HSP), as well as phase separation/crystallization data obtained from X-ray diffraction and differential scanning calorimetry. HSP calculations in some cases led to false positive predictions of tacrolimus miscibility with the tested polymers. The novel rheology-based method provided valuable insights into drug-polymer interactions and likely miscibility with polymer. It is a rather fast, inexpensive, and robust analytical approach, which could be used complementary to in silico-based evaluation of polymers in early formulation development, especially in cases of rather large active pharmaceutical ingredients. Full article

(This article belongs to the Special Issue Pharmaceutical Freeze Drying and Spray Drying)

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16 pages, 6645 KiB

Open AccessArticle

Be Aggressive! Amorphous Excipients Enabling Single-Step Freeze-Drying of Monoclonal Antibody Formulations

by Christina Haeuser, Pierre Goldbach, Joerg Huwyler, Wolfgang Friess and Andrea Allmendinger

Pharmaceutics 2019, 11(11), 616; https://doi.org/10.3390/pharmaceutics11110616 - 17 Nov 2019

Cited by 31 | Viewed by 5762

Abstract

Short freeze-drying cycles for biopharmaceuticals are desirable. Formulations containing an amorphous disaccharide, such as sucrose, are prone to collapse upon aggressive primary drying at higher shelf temperature. We used 2-hydroxypropyl-betacyclodextrin (HPBCD) in combination with sucrose and polyvinylpyrrolidone (PVP) to develop an aggressive lyophilization [...] Read more.

Short freeze-drying cycles for biopharmaceuticals are desirable. Formulations containing an amorphous disaccharide, such as sucrose, are prone to collapse upon aggressive primary drying at higher shelf temperature. We used 2-hydroxypropyl-betacyclodextrin (HPBCD) in combination with sucrose and polyvinylpyrrolidone (PVP) to develop an aggressive lyophilization cycle for low concentration monoclonal antibody (mAb) formulations. Glass transition temperature and collapse temperature of the formulations were determined, and increasingly aggressive cycle parameters were applied. Using a shelf temperature of +30 °C during primary drying, the concept of combining sublimation and desorption of water in a single drying step was investigated. Cake appearance was evaluated visually and by micro-computed tomography. Lyophilisates were further analyzed for reconstitution time, specific surface area, residual moisture, and glass transition temperature. We demonstrated the applicability of single-step freeze-drying, shortening the total cycle time by 50% and providing elegant lyophilisates for pure HPBCD and HPBCD/sucrose formulations. HPBCD/PVP/sucrose showed minor dents, while good mAb stability at 10 mg/mL was obtained for HPBCD/sucrose and HPBCD/PVP/sucrose when stored at 40 °C for 3 months. We conclude that HPBCD-based formulations in combination with sucrose are highly attractive, enabling aggressive, single-step freeze-drying of low concentration mAb formulations, while maintaining elegant lyophilisates and ensuring protein stability at the same time. Full article

(This article belongs to the Special Issue Pharmaceutical Freeze Drying and Spray Drying)

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20 pages, 5060 KiB

Open AccessArticle

Stabilization of Deformable Nanovesicles Based on Insulin-Phospholipid Complex by Freeze-Drying

by You Xu, Yiyue Guo, Yuqi Yang, Yingying Meng, Xuejun Xia and Yuling Liu

Pharmaceutics 2019, 11(10), 539; https://doi.org/10.3390/pharmaceutics11100539 - 16 Oct 2019

Cited by 6 | Viewed by 3622

Abstract

Deformable nanovesicles have been extensively investigated due to their excellent ability to penetrate biological barriers. However, suffering from serious physical and chemical instabilities, the wide use of deformable nanovesicles in medical applications is still limited. Moreover, far less work has been done to [...] Read more.

Deformable nanovesicles have been extensively investigated due to their excellent ability to penetrate biological barriers. However, suffering from serious physical and chemical instabilities, the wide use of deformable nanovesicles in medical applications is still limited. Moreover, far less work has been done to pursue the lyophilization of deformable nanovesicles. Here, we aimed to obtain stable deformable nanovesicles via freeze-drying technology and to uncover the underlying protection mechanisms. Firstly, the density of nanovesicles before freeze-drying, the effect of different kinds of cryoprotectants, and the types of different reconstituted solvents after lyophilization were investigated in detail to obtain stable deformable nanovesicles based on insulin-phospholipid complex (IPC-DNVs). To further investigate the underlying protection mechanisms, we performed a variety of analyses. We found that deformable nanovesicles at a low density containing 8% lactose and trehalose in a ratio of 1:4 (8%-L-T) have a spherical shape, smooth surface morphology in the lyophilized state, a whorl-like structure, high entrapment efficiency, and deformability after reconstitution. Importantly, the integrity of IPC, as well as the secondary structure of insulin, were well protected. Accelerated stability studies demonstrated that 8%-L-T remained highly stable during storage for 6 months at 25 °C. Based on in vivo results, lyophilized IPC-DNVs retained their bioactivity and had good efficacy. Given the convenience of preparation and long term stability, the use of combined cryoprotectants in a proper ratio to protect stable nanovesicles indicates strong potential for industrial production. Full article

(This article belongs to the Special Issue Pharmaceutical Freeze Drying and Spray Drying)

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15 pages, 2061 KiB

Open AccessArticle

Spray Drying of a Subcritical Extract Using Marrubium vulgare as a Method of Choice for Obtaining High Quality Powder

by Aleksandra Gavarić, Jelena Vladić, Rita Ambrus, Stela Jokić, Piroska Szabó-Révész, Milan Tomić, Marijana Blažić and Senka Vidović

Pharmaceutics 2019, 11(10), 523; https://doi.org/10.3390/pharmaceutics11100523 - 11 Oct 2019

Cited by 14 | Viewed by 5421

Abstract

White horehound (Marrubium vulgare L.), is a grey-leaved perennial herb, belonging to Lamiaceae family, distributed in Eurasia and northern Africa. Despite the fact that M. vulgare has been used since ancient times in treating diverse diseases, it is only in the last [...] Read more.

White horehound (Marrubium vulgare L.), is a grey-leaved perennial herb, belonging to Lamiaceae family, distributed in Eurasia and northern Africa. Despite the fact that M. vulgare has been used since ancient times in treating diverse diseases, it is only in the last decade or so that scientists have been able to lay the foundation for its potential pharmacological actions from the results observed through the prism of ethnopharmacological use of this species. The novelty of this study was that subcritical water extraction, acknowledged as a powerful extraction technology to recover phenolic compounds, was coupled with spray drying. The subcritical horehound extract, obtained using optimal process parameters, was used as a liquid feed in spray drying. Maltodextrin was used as a carrier in a concentration of 10%. Thus, two M. vulgare powders, carrier-free and 10% MD, were produced. Comprehensive powders characterization was conducted in order to evaluate their quality. Results confirmed that spray drying can be used as a method of choice for obtaining high quality horehound powders which kept the amorphous structure constant after 6 months. Full article

(This article belongs to the Special Issue Pharmaceutical Freeze Drying and Spray Drying)

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20 pages, 1874 KiB

Open AccessArticle

Long-Term Physical (In)Stability of Spray-Dried Amorphous Drugs: Relationship with Glass-Forming Ability and Physicochemical Properties

by Khadijah Edueng, Christel A.S. Bergström, Johan Gråsjö and Denny Mahlin

Pharmaceutics 2019, 11(9), 425; https://doi.org/10.3390/pharmaceutics11090425 - 21 Aug 2019

Cited by 19 | Viewed by 4257

Abstract

This study shows the importance of the chosen method for assessing the glass-forming ability (GFA) and glass stability (GS) of a drug compound. Traditionally, GFA and GS are established using in situ melt-quenching in a differential scanning calorimeter. In this study, we included [...] Read more.

This study shows the importance of the chosen method for assessing the glass-forming ability (GFA) and glass stability (GS) of a drug compound. Traditionally, GFA and GS are established using in situ melt-quenching in a differential scanning calorimeter. In this study, we included 26 structurally diverse glass-forming drugs (i) to compare the GFA class when the model drugs were produced by spray-drying with that when melt-quenching was used, (ii) to investigate the long-term physical stability of the resulting amorphous solids, and (iii) to investigate the relationship between physicochemical properties and the GFA of spray-dried solids and their long-term physical stability. The spray-dried solids were exposed to dry (<5% RH) and humid (75% RH) conditions for six months at 25 °C. The crystallization of the spray-dried solids under these conditions was monitored using a combination of solid-state characterization techniques including differential scanning calorimetry, Raman spectroscopy, and powder X-ray diffraction. The GFA/GS class assignment for 85% of the model compounds was method-dependent, with significant differences between spray-drying and melt-quenching methods. The long-term physical stability under dry condition of the compounds was predictable from GFA/GS classification and glass transition and crystallization temperatures. However, the stability upon storage at 75% RH could not be predicted from the same data. There was no strong correlation between the physicochemical properties explored and the GFA class or long-term physical stability. However, there was a slight tendency for compounds with a relatively larger molecular weight, higher glass transition temperature, higher crystallization temperature, higher melting point and higher reduced glass transition temperature to have better GFA and better physical stability. In contrast, a high heat of fusion and entropy of fusion seemed to have a negative impact on the GFA and physical stability of our dataset. Full article

(This article belongs to the Special Issue Pharmaceutical Freeze Drying and Spray Drying)

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7 pages, 2397 KiB

Open AccessArticle

Electrostatic Precipitation of Submicron Particles in a Molten Carrier

by Adrian Dobrowolski, Damian Pieloth, Helmut Wiggers and Markus Thommes

Pharmaceutics 2019, 11(6), 276; https://doi.org/10.3390/pharmaceutics11060276 - 13 Jun 2019

Cited by 6 | Viewed by 3643

Abstract

Recently, submicron particles have been discussed as a means to increase the bioavailability of poorly water-soluble drugs. Separation of these small particles is done with both fibre and membrane filters, as well as electrostatic precipitators. A major disadvantage of an electrostatic precipitator (ESP) [...] Read more.

Recently, submicron particles have been discussed as a means to increase the bioavailability of poorly water-soluble drugs. Separation of these small particles is done with both fibre and membrane filters, as well as electrostatic precipitators. A major disadvantage of an electrostatic precipitator (ESP) is the agglomerate formation on the precipitation electrode. These agglomerates frequently show low bioavailability, due to the decreased specific surface area and poor wettability. In this work, a new melt electrostatic precipitator was developed and tested to convert submicron particles into a solid dispersion in order to increase the bioavailability of active pharmaceutical ingredients. The submicron particles were generated by spray drying and transferred to the ESP, where the collection electrode is covered with a melt, which served as matrix after solidification. The newly developed melt electrostatic precipitator was able to collect isolated naproxen particles in a molten carrier. A solid naproxen xylitol dispersion was prepared, which showed a reduction of the dissolution time by 82%, and a release of 80% of the total drug, compared to the physical mixture. Full article

(This article belongs to the Special Issue Pharmaceutical Freeze Drying and Spray Drying)

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