Continuous Manufacturing and Molecular Modeling of Pharmaceutical Amorphous Solid Dispersions

Nambiar, Amritha G.; Singh, Maan; Mali, Abhishek R; Serrano, Dolores R.; Kumar, Rajnish; Healy, Anne Marie; Agrawal, Ashish Kumar; Kumar, Dinesh

doi:10.1208/s12249-022-02408-4

Cited by 22 publications

(8 citation statements)

References 188 publications

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“…This is facilitated by Process Analytical Technology (PAT). According to the Food and Drug Administration, “PAT is a system for designing, analyzing, and controlling manufacturing through timely measurements (i.e., during processing) of critical quality and performance attributes of raw and in-process materials and processes with the goal of ensuring final product quality.” Essentially, PAT provides an enhanced understanding of the unit processes and thereby facilitates process and quality improvement [ 106 , 107 ]. Various method and tools available for moisture content determination are listed in Table 6 .…”

Section: Methods and Tools For Moisture Content Determinationmentioning

confidence: 99%

Co-Crystallization Approach to Enhance the Stability of Moisture-Sensitive Drugs

et al. 2023

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Stability is an essential quality attribute of any pharmaceutical formulation. Poor stability can change the color and physical appearance of a drug, directly impacting the patient’s perception. Unstable drug products may also face loss of active pharmaceutical ingredients (APIs) and degradation, making the medicine ineffective and toxic. Moisture content is known to be the leading cause of the degradation of nearly 50% of medicinal products, leading to impurities in solid dose formulations. The polarity of the atoms in an API and the surface chemistry of API particles majorly influence the affinity towards water molecules. Moisture induces chemical reactions, including free water that has also been identified as an important factor in determining drug product stability. Among the various approaches, crystal engineering and specifically co-crystals, have a proven ability to increase the stability of moisture-sensitive APIs. Other approaches, such as changing the salt form, can lead to solubility issues, thus making the co-crystal approach more suited to enhancing hygroscopic stability. There are many reported studies where co-crystals have exhibited reduced hygroscopicity compared to pure API, thereby improving the product’s stability. In this review, the authors focus on recent updates and trends in these studies related to improving the hygroscopic stability of compounds, discuss the reasons behind the enhanced stability, and briefly discuss the screening of co-formers for moisture-sensitive drugs.

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Section: Methods and Tools For Moisture Content Determinationmentioning

confidence: 99%

Co-Crystallization Approach to Enhance the Stability of Moisture-Sensitive Drugs

et al. 2023

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“…One of the main advantages of this technique is the formation of amorphous solid dispersions that enhance the solubility of poorly water-soluble drugs and, hence, oral bioavailability [ 39 ]. Additionally, the temperature is high enough to limit the risk of microbiological contamination, and the water content is limited, enhancing long-term drug stability.…”

Section: 3d Printing Of Medicinesmentioning

confidence: 99%

3D Printing Technologies in Personalized Medicine, Nanomedicines, and Biopharmaceuticals

et al. 2023

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3D printing technologies enable medicine customization adapted to patients’ needs. There are several 3D printing techniques available, but majority of dosage forms and medical devices are printed using nozzle-based extrusion, laser-writing systems, and powder binder jetting. 3D printing has been demonstrated for a broad range of applications in development and targeting solid, semi-solid, and locally applied or implanted medicines. 3D-printed solid dosage forms allow the combination of one or more drugs within the same solid dosage form to improve patient compliance, facilitate deglutition, tailor the release profile, or fabricate new medicines for which no dosage form is available. Sustained-release 3D-printed implants, stents, and medical devices have been used mainly for joint replacement therapies, medical prostheses, and cardiovascular applications. Locally applied medicines, such as wound dressing, microneedles, and medicated contact lenses, have also been manufactured using 3D printing techniques. The challenge is to select the 3D printing technique most suitable for each application and the type of pharmaceutical ink that should be developed that possesses the required physicochemical and biological performance. The integration of biopharmaceuticals and nanotechnology-based drugs along with 3D printing (“nanoprinting”) brings printed personalized nanomedicines within the most innovative perspectives for the coming years. Continuous manufacturing through the use of 3D-printed microfluidic chips facilitates their translation into clinical practice.

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“…In the 1970s, Chiou and Riegelman defined the term solid dispersions as the dispersion of an active pharmaceutical ingredient (API) in an amorphous carrier in a solid state prepared by solvent, melting, or solvent-melting methods [ 7 ]. In these systems, there is a mixture at the molecular level between a polymer and the drug in an amorphous state, increasing its bioavailability [ 8 , 9 , 10 , 11 , 12 ]. It is known that the low thermodynamic stability due to the high energy of the amorphous state causes relaxation, nucleation, and recrystallization under different variables [ 13 , 14 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Physicochemical Characterization and In Vitro Activity of Poly(ε-Caprolactone)/Mycophenolic Acid Amorphous Solid Dispersions

Sánchez-Aguinagalde,

Sanchez-Rexach,

Polo

et al. 2024

Polymers

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The obtention of amorphous solid dispersions (ASDs) of mycophenolic acid (MPA) in poly(ε-caprolactone) (PCL) is reported in this paper. An improvement in the bioavailability of the drug is possible thanks to the favorable specific interactions occurring in this system. Differential scanning calorimetry (DSC) was used to investigate the miscibility of PCL/MPA blends, measuring glass transition temperature (Tg) and analyzing melting point depression to obtain a negative interaction parameter, which indicates the development of favorable inter-association interactions. Fourier transform infrared spectroscopy (FTIR) was used to analyze the specific interaction occurring in the blends. Drug release measurements showed that at least 70% of the drug was released by the third day in vitro in all compositions. Finally, preliminary in vitro cell culture experiments showed a decreased number of cancerous cells over the scaffolds containing MPA, presumably arising from the anti-cancer activity attributable to MPA.

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Continuous Manufacturing and Molecular Modeling of Pharmaceutical Amorphous Solid Dispersions

Cited by 22 publications

References 188 publications

Co-Crystallization Approach to Enhance the Stability of Moisture-Sensitive Drugs

Co-Crystallization Approach to Enhance the Stability of Moisture-Sensitive Drugs

3D Printing Technologies in Personalized Medicine, Nanomedicines, and Biopharmaceuticals

Physicochemical Characterization and In Vitro Activity of Poly(ε-Caprolactone)/Mycophenolic Acid Amorphous Solid Dispersions

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