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Pharmaceutics
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Advances in Pharmaceutical Solid Forms
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Advances in Pharmaceutical Solid Forms

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Physical Pharmacy and Formulation".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 18513

Special Issue Editor

Prof. Dr. Yohann Corvis

E-Mail Website
Guest Editor
School of Pharmacy, Faculté de Santé—Université de Paris, 4, Avenue de l'Observatoire, 75 006 Paris, France
Interests: solid state chemistry; co-crystal science; active pharmaceutical ingredient and excipient stability; polymorphs screening; nanomedicine; drug formulation; physical chemistry of pharmaceutical ingredients; pharmacokinetics; in vitro dissolution studies; nanocrystals; nanoemulsions

Special Issue Information

Dear Colleagues,

Solubility enhancement of poorly water-soluble drugs is a major challenge in the pharmaceutical field since 80% of the marketed drugs are formulated in solid state and more than 70% of the drugs in development exhibit low solubility (BCS class II and IV). Nevertheless, solid dosage forms are widely favored, mainly due to stability issues of the active ingredients.

A broad and comprehensive study of various solid forms of the pharmaceutical matter is needed to enhance their clinical translation with optimized success. Indeed, the most suitable solid forms have to be taken into consideration regarding their stability and bioavailability.

Many matter modification processes in the solid state, such as salts, solid solutions, scalemic mixtures, amorphous, polymorphs, solvatomorphs, nanocrystals, guest-host assemblies, nanocarriers, and cocrystals formation, have been adapted to challenge and improve both drug substance loading capacity and bioavailability. Each system presents its own advantages and drawbacks, depending on the administration route, the therapeutic target, the release rate of the drug, the final product manufacturing, and the cost of production; the objective behind this survey is to enhance the benefice/risk ratio of innovative formulation for adaptative treatments.

Reviews and original articles dealing with the modulation of pharmaceutical solid dosage forms (with organic or inorganic active ingredients) for formulation, storage, and therapeutic effect enhancement are encouraged for publication in this Special Issue of Pharmaceutics.

Prof. Dr. Yohann Corvis
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • salt formation
  • solvate/hydrate formation
  • size reduction
  • polymorphism
  • amorphisation
  • solid solutions
  • solid suspensions
  • enantiomeric vs. racemic drugs
  • active ingredient: excipient interactions
  • active ingredient: active ingredient interactions

Published Papers (7 papers)

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Research

24 pages, 36806 KiB  
Article
New Lidocaine-Based Pharmaceutical Cocrystals: Preparation, Characterization, and Influence of the Racemic vs. Enantiopure Coformer on the Physico-Chemical Properties
by Panpan Ma, Balthazar Toussaint, Enrica Angela Roberti, Noémie Scornet, Axel Santos Silva, Luis Castillo Henríquez, Monique Cadasse, Philippe Négrier, Stéphane Massip, Hanh Dufat, Karim Hammad, Cecilia Baraldi, Maria Cristina Gamberini, Cyrille Richard, Stéphane Veesler, Philippe Espeau, Tu Lee and Yohann Corvis
Pharmaceutics 2023, 15(4), 1102; https://doi.org/10.3390/pharmaceutics15041102 - 29 Mar 2023
Cited by 1 | Viewed by 3013
Abstract
This study describes the preparation, characterization, and influence of the enantiopure vs. racemic coformer on the physico-chemical properties of a pharmaceutical cocrystal. For that purpose, two new 1:1 cocrystals, namely lidocaine:dl-menthol and lidocaine:d-menthol, were prepared. The menthol racemate-based cocrystal [...] Read more.
This study describes the preparation, characterization, and influence of the enantiopure vs. racemic coformer on the physico-chemical properties of a pharmaceutical cocrystal. For that purpose, two new 1:1 cocrystals, namely lidocaine:dl-menthol and lidocaine:d-menthol, were prepared. The menthol racemate-based cocrystal was evaluated by means of X-ray diffraction, infrared spectroscopy, Raman, thermal analysis, and solubility experiments. The results were exhaustively compared with the first menthol-based pharmaceutical cocrystal, i.e., lidocaine:l-menthol, discovered in our group 12 years ago. Furthermore, the stable lidocaine/dl-menthol phase diagram has been screened, thoroughly evaluated, and compared to the enantiopure phase diagram. Thus, it has been proven that the racemic vs. enantiopure coformer leads to increased solubility and improved dissolution of lidocaine due to the low stable form induced by menthol molecular disorder in the lidocaine:dl-menthol cocrystal. To date, the 1:1 lidocaine:dl-menthol cocrystal is the third menthol-based pharmaceutical cocrystal, after the 1:1 lidocaine:l-menthol and the 1:2 lopinavir:l-menthol cocrystals reported in 2010 and 2022, respectively. Overall, this study shows promising potential for designing new materials with both improved characteristics and functional properties in the fields of pharmaceutical sciences and crystal engineering. Full article
(This article belongs to the Special Issue Advances in Pharmaceutical Solid Forms)
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18 pages, 1166 KiB  
Article
Downstream Processing of Amorphous and Co-Amorphous Olanzapine Powder Blends
by Nuno F. da Costa, Rolf Daniels, Ana I. Fernandes and João F. Pinto
Pharmaceutics 2022, 14(8), 1535; https://doi.org/10.3390/pharmaceutics14081535 - 23 Jul 2022
Cited by 6 | Viewed by 2167
Abstract
The work evaluates the stability of amorphous and co-amorphous olanzapine (OLZ) in tablets manufactured by direct compression. The flowability and the compressibility of amorphous and co-amorphous OLZ with saccharin (SAC) and the properties of the tablets obtained were measured and compared to those [...] Read more.
The work evaluates the stability of amorphous and co-amorphous olanzapine (OLZ) in tablets manufactured by direct compression. The flowability and the compressibility of amorphous and co-amorphous OLZ with saccharin (SAC) and the properties of the tablets obtained were measured and compared to those of tablets made with crystalline OLZ. The flowability of the amorphous and mostly of the co-amorphous OLZ powders decreased in comparison with the crystalline OLZ due to the higher cohesiveness of the former materials. The stability of the amorphous and co-amorphous OLZ prior to and after tableting was monitored by XRPD, FTIR, and NIR spectroscopies. Tablets presented long-lasting amorphous OLZ with enhanced water solubility, but the release rate of the drug decreased in comparison with tablets containing crystalline OLZ. In physical mixtures made of crystalline OLZ and SAC, an extent of amorphization of approximately 20% was accomplished through the application of compaction pressures and dwell times of 155 MPa and 5 min, respectively. The work highlighted the stability of amorphous and co-amorphous OLZ during tableting and the positive effect of compaction pressure on the formation of co-amorphous OLZ, providing an expedited amorphization technique, given that the process development-associated hurdles were overcome. Full article
(This article belongs to the Special Issue Advances in Pharmaceutical Solid Forms)
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28 pages, 4445 KiB  
Article
Crystallization of Form II Paracetamol with the Assistance of Carboxylic Acids toward Batch and Continuous Processes
by Kuan-Lin Yeh, Hung-Lin Lee and Tu Lee
Pharmaceutics 2022, 14(5), 1099; https://doi.org/10.3390/pharmaceutics14051099 - 20 May 2022
Cited by 3 | Viewed by 2188
Abstract
Form II paracetamol has captured the interest of researchers due to its improved compressibility. However, its low stability has made it difficult to be produced on a large scale with good reproducibility. In the present study, the selective polymorphic formation of paracetamol was [...] Read more.
Form II paracetamol has captured the interest of researchers due to its improved compressibility. However, its low stability has made it difficult to be produced on a large scale with good reproducibility. In the present study, the selective polymorphic formation of paracetamol was carried out by cooling crystallization with four types of additives: adipic acid, fumaric acid, oxalic acid, and succinic acid. It was found that: (1) the more additives that were added, the higher the probability of forming Form II paracetamol; (2) Form II paracetamol could be induced by seeding the paracetamol aqueous solution with Form II paracetamol and fumaric acid crystals, and not the other three carboxylic acids; (3) a new solution complex of paracetamol–oxalic acid, evidenced by the solubility diagram, was responsible for the selective nucleation of Form II paracetamol in the oxalic acid aqueous solution; and (4) the range of the degree of supersaturation for nucleating Form II paracetamol was extended with the assistance of oxalic acid or fumaric acid. In large-scale crystallization, Form II paracetamol was produced by the continuous crystallization of 44 mg of paracetamol/mL in 50 wt% of fumaric acid aqueous solution with a flow rate of 150 mL/min. Full article
(This article belongs to the Special Issue Advances in Pharmaceutical Solid Forms)
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18 pages, 5196 KiB  
Article
Comparison of Paliperidone Palmitate from Different Crystallization Processes and Effect on Formulations In Vitro and In Vivo
by Junfeng Shi, Dan Wang, Yang Tian, Zengming Wang, Jing Gao, Nan Liu, Xiang Gao, Aiping Zheng, Hui Zhang and Meixian Xiang
Pharmaceutics 2022, 14(5), 1094; https://doi.org/10.3390/pharmaceutics14051094 - 20 May 2022
Cited by 3 | Viewed by 2712
Abstract
The quality of active pharmaceutical ingredients (APIs) is an important factor which can affect the safety and efficacy of pharmaceuticals. This study was designed to investigate the nature of paliperidone palmitate (PP) obtained by different crystallization processes, then compare the characteristics between test [...] Read more.
The quality of active pharmaceutical ingredients (APIs) is an important factor which can affect the safety and efficacy of pharmaceuticals. This study was designed to investigate the nature of paliperidone palmitate (PP) obtained by different crystallization processes, then compare the characteristics between test formulations which prepared PP of different crystallization and reference formulations (Invega Sustenna®) in vitro and in vivo. Two different PPs, namely PP-1 and PP-2, were prepared by different crystallization methods. Contact angle, morphology, and crystallinity of the PPs were characterized. Taking the particle sizes and distribution of Invega Sustenna® as reference, test formulations were prepared by the wet milling method using either a PP-1 or PP-2 sample. Their release behavior, stability in vitro, and pharmacokinetics in vivo were subsequently investigated. The results indicated that PP-2 had a higher surface free energy (SFE). More small particles were attached to the PP-1 surface under the influence of crystallization temperature. Different crystallization processes did not change the crystal of PP, but changed the crystallinity of PP. There was no obvious difference in in vitro releases between test formulations. However, the stability and state of formulation containing PP-2 were better compared to formulations containing PP-1, indicated by differences in crystallinity and SFE. Meanwhile, pharmacokinetic in vivo results demonstrated that the pharmacokinetic profiles and parameters of formulation containing PP-2 and Invega Sustenna® tended to be consistent, but those of formulations containing PP-1 were significantly different from those of formulations containing PP-2 or Invega Sustenna®, and there was burst release phenomenon of formulations containing PP-1 in rats. PP made by different crystallization processes could induce changes in appearance, SFE, and crystallinity, and further affect the stability, state, and pharmacokinetic in vivo formulation. Full article
(This article belongs to the Special Issue Advances in Pharmaceutical Solid Forms)
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14 pages, 4044 KiB  
Article
Preformulation Studies of Ezetimibe-Simvastatin Solid Dispersions in the Development of Fixed-Dose Combinations
by Agata Górniak, Adrianna Złocińska, Mateusz Trojan, Adrianna Pęcak and Bożena Karolewicz
Pharmaceutics 2022, 14(5), 912; https://doi.org/10.3390/pharmaceutics14050912 - 22 Apr 2022
Cited by 4 | Viewed by 2295
Abstract
Two active pharmaceutical ingredients (APIs) with limited solubility, simvastatin and ezetimibe, prepared as a drug-drug solid dispersion (SD) was evaluated for physicochemical, microstructural, and aqueous dissolution properties. The simvastatin-ezetimibe SD was prepared using the co-grinding method in a wide range of weight fractions [...] Read more.
Two active pharmaceutical ingredients (APIs) with limited solubility, simvastatin and ezetimibe, prepared as a drug-drug solid dispersion (SD) was evaluated for physicochemical, microstructural, and aqueous dissolution properties. The simvastatin-ezetimibe SD was prepared using the co-grinding method in a wide range of weight fractions and differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) were used to perform the phase composition analysis. DSC studies confirmed that simvastatin and ezetimibe form a simple eutectic phase equilibrium diagram. Analysis of Fourier transform infrared spectroscopy (FTIR) studies excluded strong interactions between the APIs. Our investigations have revealed that all studied dispersions are characterized by substantially improved ezetimibe dissolution regardless of simvastatin content, and are best when the composition oscillates near the eutectic point. Data obtained in our studies provide an opportunity for the development of well-formulated, ezetimibe-simvastatin fixed-dose combinations (for hypercholesterolemia treatment) with reduced ezetimibe dosages based on its dissolution improvement. Full article
(This article belongs to the Special Issue Advances in Pharmaceutical Solid Forms)
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17 pages, 3226 KiB  
Article
Clathrate Hydrates of Organic Solvents as Auxiliary Intermediates in Pharmaceutical Research and Development: Improving Dissolution Behaviour of a New Anti-Tuberculosis Drug, Perchlozon
by Andrey G. Ogienko, Svetlana A. Myz, Andrey A. Nefedov, Anna A. Ogienko, Tatyana P. Adamova, Olga M. Voronkova, Svetlana V. Amosova, Boris A. Trofimov, Vladimir V. Boldyrev and Elena V. Boldyreva
Pharmaceutics 2022, 14(3), 495; https://doi.org/10.3390/pharmaceutics14030495 - 24 Feb 2022
Cited by 1 | Viewed by 2157
Abstract
There is an urgent need for new drugs to overcome the challenge of the ever-growing drug resistance towards tuberculosis. A new, highly efficient anti-tuberculosis drug, Perchlozone (thioureidoiminomethylpyridinium perchlorate, Pz), is only available in an oral dosage form, though injectable forms and inhalation solutions [...] Read more.
There is an urgent need for new drugs to overcome the challenge of the ever-growing drug resistance towards tuberculosis. A new, highly efficient anti-tuberculosis drug, Perchlozone (thioureidoiminomethylpyridinium perchlorate, Pz), is only available in an oral dosage form, though injectable forms and inhalation solutions could be better alternatives, offering higher bioavailability. To produce such forms, nano- and micro-particles of APIs would need to be prepared as dispersions with carriers. We use this case study to illustrate the principles of selecting solvents and excipients when preparing such formulations. We justify the choice of water–THF (19.1 wt % THF) as solvent and mannitol as carrier to prepare formulations of Pz—a poorly soluble compound—that are suitable for injection or inhalation. The formulations could be prepared by conventional freeze-drying in vials, making the proposed method suitable for industrial scaling. A similar strategy for selecting the organic solvent and the excipient can be applied to other compounds with low water solubility. Full article
(This article belongs to the Special Issue Advances in Pharmaceutical Solid Forms)
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11 pages, 1838 KiB  
Article
Eutectic Formation of Naproxen with Some Dicarboxylic Acids
by Dahye Kim, Soeun Jang and Il Won Kim
Pharmaceutics 2021, 13(12), 2081; https://doi.org/10.3390/pharmaceutics13122081 - 04 Dec 2021
Cited by 4 | Viewed by 1817
Abstract
Eutectic formation with additives is one of the established methods to improve the dissolution behaviors of active pharmaceutic ingredients (APIs). The improvement is mainly due to the increase in the surface area for dissolution, which originates from the finely divided micro-domains generated through [...] Read more.
Eutectic formation with additives is one of the established methods to improve the dissolution behaviors of active pharmaceutic ingredients (APIs). The improvement is mainly due to the increase in the surface area for dissolution, which originates from the finely divided micro-domains generated through the phase separation of the miscible liquid components upon solidification. The present study is to identify eutectic-forming additives for naproxen (NPX), a class II API of the biopharmaceutical classification system. A particular aim was to develop a eutectic mixture with NPX at least over 20 wt%, a minimum to be practical for oral delivery. Screening based on the proximity of the solubility parameter values identified dicarboxylic acids (succinic acid, glutaric acid, and suberic acid) as desirable additives for NPX. Binary melting diagrams were constructed to confirm the eutectic compositions, and the eutectic mixture with suberic acid (NPX 55 wt%) was further investigated. The dissolution (at pH 5.0) of the melt crystallized eutectics was enhanced compared to the simple physical mixture of the same compositions and neat NPX, which was attributed to the microscopically observed lamellar structures. The current study should support the systematic investigations of API eutectic mixtures by selecting appropriate eutectic-forming additives. Full article
(This article belongs to the Special Issue Advances in Pharmaceutical Solid Forms)
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