Continuous Formulation Approaches of Amorphous Solid Dispersions: Significance of Powder Flow Properties and Feeding Performance

Szabó, Edina; Démuth, Balázs; Galata, Dorián László; Vass, Panna; Hirsch, Edit; Csontos, István; Marosi, György; Nagy, Zsombor Kristóf

doi:10.3390/pharmaceutics11120654

Cited by 23 publications

(23 citation statements)

References 127 publications

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“…All fresh extrudates showed adequate rheological characteristics for pharmaceutical production (gray bars of Figure 6 a), with compressibility values below 20% [ 44 ] and considerable improvement of the deficient flow characteristics of paracetamol as supplied. In fact, the HME process promotes the densification of the solid material, and the plastic polymer matrix favors the cut in the granulation process originating free-flow particles [ 45 , 46 ].…”

Section: Resultsmentioning

confidence: 99%

Hot-Melt Extrusion as an Advantageous Technology to Obtain Effervescent Drug Products

et al. 2020

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Here, we assessed the feasibility of hot-melt extrusion (HME) to obtain effervescent drug products for the first time. For this, a combined mixture design was employed using paracetamol as a model drug. Extrudates were obtained under reduced torque (up to 0.3 Nm) at 100 °C to preserve the stability of the effervescent salts. Formulations showed vigorous and rapid effervescent disintegration (<3 min), adequate flow characteristics, and complete solubilization of paracetamol instantly after the effervescent reaction. Formulations containing PVPVA in the concentration range of 15–20% m/m were demonstrated to be sensitive to accelerated aging conditions, undergoing marked microstructural changes, since the capture of water led to the agglomeration and loss of their functional characteristics. HPMC matrices, in contrast, proved to be resistant to storage conditions in high relative humidity, showing superior performance to controls, including the commercial product. Moreover, the combined mixture design allowed us to identify significant interactions between the polymeric materials and the disintegrating agents, showing the formulation regions in which the responses are kept within the required levels. In conclusion, this study demonstrates that HME can bring important benefits to the elaboration of effervescent drug products, simplifying the production process and obtaining formulations with improved characteristics, such as faster disintegration, higher drug solubilization, and better stability.

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Section: Resultsmentioning

confidence: 99%

Hot-Melt Extrusion as an Advantageous Technology to Obtain Effervescent Drug Products

et al. 2020

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“…Downstream processing of ASDs, typically consisting of feeding, blending and tableting, can have an impact on the physical stability of ASDs by influencing the environmental factors, as described in Section 2.1.3, as well as the content uniformity of final products, as reviewed in detail by various research groups [6,38]. The latter issue with content uniformity is mainly ascribed to the poor flow properties of bulk ASD powders for further processing.…”

Section: Downstream Processing Issues Of Asdsmentioning

confidence: 99%

“…The latter issue with content uniformity is mainly ascribed to the poor flow properties of bulk ASD powders for further processing. In this regard, current studies tend to focus on alternative manufacturing strategies such as electrospinning, HME-injection molding and an HME-3D printing combination, but the application of such approaches is often limited by the poor scalability as compared to traditional formulation lines [6,39].…”

Section: Downstream Processing Issues Of Asdsmentioning

confidence: 99%

“…ASDs are regarded as one of the most promising and efficient techniques for the solubilization of poorly water soluble APIs [3,4]. ASDs have been widely studied, and there have been a huge number of high quality reviews summarizing the development and research progress of ASDs [5][6][7][8][9][10][11]. Thus, this review only provides a very brief introduction to ASDs, which leads to the main focus of the review, i.e., microwave induced in situ amorphization, as an upcoming approach to solving the physical stability concerns of ASDs.…”

Section: Introductionmentioning

confidence: 99%

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Microwave-Induced In Situ Amorphization: A New Strategy for Tackling the Stability Issue of Amorphous Solid Dispersions

et al. 2020

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The thermodynamically unstable nature of amorphous drugs has led to a persistent stability issue of amorphous solid dispersions (ASDs). Lately, microwave-induced in situ amorphization has been proposed as a promising solution to this problem, where the originally loaded crystalline drug is in situ amorphized within the final dosage form using a household microwave oven prior to oral administration. In addition to circumventing issues with physical stability, it can also simplify the problematic downstream processing of ASDs. In this review paper, we address the significance of exploring and developing this novel technology with an emphasis on systemically reviewing the currently available literature in this pharmaceutical arena and highlighting the underlying mechanisms involved in inducing in situ amorphization. Specifically, in order to achieve a high drug amorphicity, formulations should be composed of drugs with high solubility in polymers, as well as polymers with high hygroscopicity and good post-plasticized flexibility of chains. Furthermore, high microwave energy input is considered to be a desirable factor. Lastly, this review discusses challenges in the development of this technology including chemical stability, selection criteria for excipients and the dissolution performance of the microwave-induced ASDs.

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“…The flow properties of ASD powder are considered critical to the quality of the final formulation [57]. In general, CI < 20 represents a free flowing nature [58].…”

Section: Drug Content and Flowabilitymentioning

confidence: 99%

Bioavailability Improvement of Carbamazepine via Oral Administration of Modified-Release Amorphous Solid Dispersions in Rats

Zhang

Xiong

et al. 2020

Pharmaceutics

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The purpose of this study was to improve the bioavailability of carbamazepine (CBZ), a poorly water-soluble antiepileptic drug, via modified-release amorphous solid dispersions (mr-ASD) by a thin film freezing (TFF) process. Three types of CBZ-mr-ASD with immediate-, delayed-, and controlled-release properties were successfully prepared with HPMC E3 (hydrophilic), L100-55 (enteric), and cellulose acetate (CA, lipophilic), defined as CBZ-ir-ASD, CBZ-dr-ASD, and CBZ-cr-ASD, respectively. A dry granulation method was used to prepare CBZ-mr-ASD capsule formulations. Various characterization techniques were applied to evaluate the physicochemical properties of CBZ-mr-ASD and the related capsules. The drug remained in an amorphous state when encapsulated within CBZ-mr-ASD, and the capsule formulation progress did not affect the performance of the dispersions. In dissolution tests, the preparations and the corresponding dosage forms similarly showed typical immediate-, delayed-, and controlled-release properties depending on the solubility of the polymers. Moreover, single-dose 24 h pharmacokinetic studies in rats indicated that CBZ-mr-ASD significantly enhanced the oral absorption of CBZ compared to that of crude CBZ. Increased oral absorption of CBZ was observed, especially in the CBZ-dr-ASD formulation, which showed a better pharmacokinetic profile than that of crude CBZ with 2.63- and 3.17-fold improved bioavailability of the drug and its main active metabolite carbamazepine 10,11-epoxide (CBZ-E).

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Continuous Formulation Approaches of Amorphous Solid Dispersions: Significance of Powder Flow Properties and Feeding Performance

Cited by 23 publications

References 127 publications

Hot-Melt Extrusion as an Advantageous Technology to Obtain Effervescent Drug Products

Hot-Melt Extrusion as an Advantageous Technology to Obtain Effervescent Drug Products

Microwave-Induced In Situ Amorphization: A New Strategy for Tackling the Stability Issue of Amorphous Solid Dispersions

Bioavailability Improvement of Carbamazepine via Oral Administration of Modified-Release Amorphous Solid Dispersions in Rats

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