Approaches for developing acyclovir gastro-retentive formulations using hot melt extrusion technology

Zhang, Peilun; Shadambikar, Gauri; Almutairi, Mashan; Bandari, Suresh; Repka, Michael A.

doi:10.1016/j.jddst.2020.102002

Cited by 17 publications

(8 citation statements)

References 29 publications

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“…In the case of air, we noticed a 12% decrease in density, which was enough to achieve the buoyancy of the composition from zero minutes. This decrease in density was less than in the case of previous results with high agitation or hot-melt extrusion [21][22][23]31,32]. In the case of two pure gases, CO2 and He, the foaming was moderate or negligible, which is well reflected in the different contact angle results.…”

Section: Discussionmentioning

confidence: 54%

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Preparation of Acyclovir-Containing Solid Foam by Ultrasonic Batch Technology

et al. 2021

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In recent years, the application of solid foams has become widespread. Solid foams are not only used in the aerospace field but also in everyday life. Although foams are promising dosage forms in the pharmaceutical industry, their usage is not prevalent due to decreased stability of the solid foam structure. These special dosage forms can result in increased bioavailability of drugs. Low-density floating formulations can also increase the gastric residence time of drugs; therefore, drug release will be sustained. Our aim was to produce a stable floating formula by foaming. Matrix components, PEG 4000 and stearic acid type 50, were selected with the criteria of low gastric irritation, a melting range below 70 °C, and well-known use in oral drug formulations. This matrix was melted at 54 °C in order to produce a dispersion of active substance and was foamed by different gases at atmospheric pressure using an ultrasonic homogenizer. The density of the molded solid foam was studied by the pycnometer method, and its structure was investigated by SEM and micro-CT. The prolonged drug release and mucoadhesive properties were proved in a pH 1.2 buffer. According to our experiments, a stable foam could be produced by rapid homogenization (less than 1 min) without any surfactant material.

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Section: Discussionmentioning

confidence: 54%

“…The technology is transferable to pharmaceutical science and compatible with numerous polymers [30]. There is a limited number of similar methods in the literature for the preparation of a low-density gastroretentive composition based on melt formation [21][22][23]31,32].…”

Section: Discussionmentioning

confidence: 99%

Preparation of Acyclovir-Containing Solid Foam by Ultrasonic Batch Technology

et al. 2021

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“…Texture analysis results of the dry, foamed composition at 25°C (0 min) and wetting coupled texture analysis result of the immersed samples at 37°C after 0.5 h, 1 h, 2 h, and 4 h. X-axis shows the time of the movement of the compression test probe [19]. On the other hand, compared to other molten gas technologies, like hot melt extrusion with CO 2 , our achieved density was higher [30]. The microCT image clearly shows the white BaSO 4 particles [31] which have a high X-ray absorption [32].…”

Section: Discussionmentioning

confidence: 97%

Process Optimization for the Continuous Production of a Gastroretentive Dosage Form Based on Melt Foaming

et al. 2021

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Several drugs have poor oral bioavailability due to low or incomplete absorption which is affected by various effects as pH, motility of GI, and enzyme activity. The gastroretentive drug delivery systems are able to deal with these problems by prolonging the gastric residence time, while increasing the therapeutic efficacy of drugs. Previously, we developed a novel technology to foam hot and molten dispersions on atmospheric pressure by a batch-type in-house apparatus. Our aim was to upgrade this technology by a new continuous lab-scale apparatus and confirm that our formulations are gastroretentive. At first, we designed and built the apparatus and continuous production was optimized using a Box–Behnken experimental design. Then, we formulated barium sulfate-loaded samples with the optimal production parameters, which was suitable for in vivo imaging analysis. In vitro study proved the low density, namely 507 mg/cm3, and the microCT record showed high porosity with 40 μm average size of bubbles in the molten suspension. The BaSO4-loaded samples showed hard structure at room temperature and during the wetting test, the complete wetting was detected after 120 min. During the in vivo study, the X-ray taken showed the retention of the formulation in the rat stomach after 2 h. We can conclude that with our device low-density floating formulations were prepared with prolonged gastric residence time. This study provides a promising platform for marketed active ingredients with low bioavailability.

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“…This process offers many advantages over conventional pharmaceutical manufacturing processes. Because it eliminates the use of solvents, it provides environmental advantages along with shorter and efficient processing time to produce the final product ( Repka et al, 2007 ; Zhang et al, 2020 ). Hence, HME has emerged as an innovative technology to produce pharmaceutical dosage forms such as tablets, capsules, implants, and films over traditional techniques ( Kallakunta et al, 2019 ; Repka et al, 2008 ; Shadambikar et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Formulation development of itraconazole PEGylated nano-lipid carriers for pulmonary aspergillosis using hot-melt extrusion technology

Shadambikar

Marathe

et al. 2021

International Journal of Pharmaceutics: X

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Pulmonary delivery is a promising alternative for the oral treatment of pulmonary aspergillosis. This study aimed to develop continuous and scalable itraconazole PEGylated nano-lipid carriers (ITZ-PEG-NLC) for inhalation delivery. The feasibility of preparing NLCs utilizing hot-melt extrusion (HME) coupled with probe sonication was investigated. The process parameters for HME and sonication were varied to optimize the formulation. ITZ-PEG-NLC (particle size, 101.20 ± 1.69 nm; polydispersity index, 0.26 ± 0.01) was successfully formulated. The drug entrapment efficiency of ITZ-PEG-NLC was 97.28 ± 0.50%. Transmission electron microscopy was used to characterize the shape of the particles. The developed formulations were evaluated for their aerodynamic properties for pulmonary delivery. The lung deposition of ITZ-PEG-NLC was determined using an Anderson Cascade Impactor and Philips Respironics Sami the Seal Nebulizer Compressor. In vitro cytotoxicity studies were performed using A549 cells. A burst-release pattern was observed in ITZ-PEG-NLC with a drug release of 41.74 ± 1.49% in 60 min. The in vitro aerosolization of the ITZ-PEG-NLC formulation showed a mass median aerodynamic diameter of 3.51 ± 0.28 μm and a geometric standard deviation of 2.44 ± 0.49. These findings indicate that HME technology could be used for the production of continuous scalable ITZ-PEG-NLC.

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Approaches for developing acyclovir gastro-retentive formulations using hot melt extrusion technology

Cited by 17 publications

References 29 publications

Preparation of Acyclovir-Containing Solid Foam by Ultrasonic Batch Technology

Preparation of Acyclovir-Containing Solid Foam by Ultrasonic Batch Technology

Process Optimization for the Continuous Production of a Gastroretentive Dosage Form Based on Melt Foaming

Formulation development of itraconazole PEGylated nano-lipid carriers for pulmonary aspergillosis using hot-melt extrusion technology

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