Over the past decades, a large number of drugs as well as drug candidates with poor dissolution characteristics have been witnessed, which invokes great interest in enabling formulation of these active ingredients. Poorly water-soluble drugs, especially biopharmaceutical classification system (BCS) II ones, are preferably designed as oral dosage forms if the dissolution limit can be broken through. Minimizing a drug’s size is an effective means to increase its dissolution and hence the bioavailability, which can be achieved by specialized dispersion techniques. This article reviews the most commonly used dispersion techniques for pharmaceutical processing that can practically enhance the dissolution and bioavailability of poorly water-soluble drugs. Major interests focus on solid dispersion, lipid-based dispersion (nanoencapsulation), and liquisolid dispersion (drug solubilized in a non-volatile solvent and dispersed in suitable solid excipients for tableting or capsulizing), covering the formulation development, preparative technique and potential applications for oral drug delivery. Otherwise, some other techniques that can increase the dispersibility of a drug such as co-precipitation, concomitant crystallization and inclusion complexation are also discussed. Various dispersion techniques provide a productive platform for addressing the formulation challenge of poorly water-soluble drugs. Solid dispersion and liquisolid dispersion are most likely to be successful in developing oral dosage forms. Lipid-based dispersion represents a promising approach to surmounting the bioavailability of low-permeable drugs, though the technique needs to traverse the obstacle from liquid to solid transformation. Novel dispersion techniques are highly encouraged to develop for formulation of poorly water-soluble drugs.

https://www.mdpi.com/1999-4923/10/3/74/pdf

Pharmaceutical Dispersion Techniques for Dissolution and Bioavailability Enhancement of Poorly Water-Soluble Drugs

Risperidone solid dispersion for orally disintegrating tablet: its formulation design and non-destructive methods of evaluation.

The discovery of cyclosporine A was a milestone in organ transplantation and the treatment of autoimmune diseases. However, developing an efficient oral delivery system for this drug is complicated by its poor biopharmaceutical characteristics (low solubility and permeability) and the need to carefully monitor its levels in the blood. Current research is exploring various approaches, including those based on emulsions, microspheres, nanoparticles, and liposomes. Although progress has been made, none of the formulations is flawless. This review is a brief description of the main pharmaceutical systems and devices that have been described for the oral delivery of cyclosporine A in the context of the physicochemical properties of the drug and the character of its interactions with lipid membranes.

https://www.degruyter.com/downloadpdf/j/cmble.2009.14.issue-1/s11658-008-0041-6/s11658-008-0041-6.xml

Oral cyclosporine A--the current picture of its liposomal and other delivery systems.

Effects of polyoxyethylene (40) stearate on the activity of P-glycoprotein and cytochrome P450.

Formulation of cyclodextrin inclusion complex-based orally disintegrating tablet of eslicarbazepine acetate for improved oral bioavailability

We experimentally demonstrated a 5-channel 125-GHz-grid wavelength division multiplexing (WDM) transmission over 6,400-km Raman amplified ultra large effective area fiber (ULAF) with 848-Gbps/carrier line-rate and 640-Gbps/carrier net-bit-rate. Our transmission is based on probabilistically shaped (PS) dual-polarization 16-ary quadrature-amplitude-modulation (16QAM) considering 25%-overhead low-density parity-check threshold of 4.6 × 10−2 bit-error-rate. By utilizing a high-speed digital-analog-converter (DAC) with a 3-dB bandwidth of 35 GHz and innovative pre-equalization based on 4-level pulse-amplitude-modulation (PAM4), 106-Gbaud 16QAM signal is reliably generated and transmitted. Besides, the transmission distance is improved obviously by using ULAF and Raman amplifier. Our results show that the PS-16QAM outperforms the regular-16QAM by around 1.5-dB sensitivity gain and 33% transmission-distance improvement. Furthermore, we have successfully applied Volterra nonlinear equalization (VNLE) to ultra-long-haul coherent optical transmission and proposed a modified offline digital-signal-processing process. By utilizing VNLE, another 15% reach improvement is obtained for PS-16QAM signal. Our work can provide an effective solution for a 600G+ ultra-long-haul transmission. As we know, this is the first time to achieve 640-Gbps/carrier WDM transmission over 6,400 km based on 106-Gbaud PS-16QAM.

640-Gbps/Carrier WDM Transmission over 6,400 km Based on PS-16QAM at 106 Gbaud Employing Advanced DSP

A solid dispersion containing cyclosporine A (CyA) and polyoxyethylene (40) stearate (PS) was prepared by the solvent-melt method and characterized by powder X-ray diffraction (PXRD), hot-stage microscopy (HSM), scanning electron microscopy (SEM) and dissolution studies. The crystalline peaks of CyA disappeared in the PXRD spectra of solid dispersions but were seen in those of physical mixtures, demonstrating the amorphous state of the drug in solid dispersions. The solubility of CyA in aqueous solutions of PS was increased linearly with increasing amount of PS in water. Dissolution of the drug from solid dispersions and physical mixtures was dramatically enhanced compared to the drug powder alone in water at 37 degrees C.

Enhancement of dissolution of cyclosporine A using solid dispersions with polyoxyethylene (40) stearate.

We provided a feasible solution for 800-Gb/s per carrier long-distance wavelength division multiplexing (WDM) coherent optical fibre transmission based on offline DSP. We experimentally demonstrate 5-carrier 125-GHz-spacing WDM coherent optical fibre transmission achieving 2000-km transmission distance and 800-Gb/s net bit rate per carrier. We utilized 100-Gbaud truncated probabilistically shaped (TPS) polarization-multiplexed 64QAM format in this work. In terms of advanced components, the high-speed digital-to-analog converter with 35-GHz 3 dB-bandwidth and Raman-amplified ultra-large-area fibre were utilized to achieve higher baud-rate and longer transmission distance. In terms of modulation format, we changed PS to TPS to obtain a more suitable shaping depth, and make the shaped signal better suited to the DSP process of coherent optical communication, including constant modulus algorithm (CMA) equalizer. Besides, our results show that the TPS-64QAM signal with 5-bit/symbol/polarization entropy outperforms the standard-32QAM with a same bit rate by around 1 dB sensitivity gain. Furthermore, we proposed a multiple-input multiple-output (MIMO) Volterra equalizer (VE), which consists of a 1st-order 2 × 2 MIMO complex-valued widely linear (WL) equalizer and a 2nd-order real-valued nonlinear equalizer. Our proposed MIMO VE can effectively resolve the impact of In-phase/quadrature (IQ) imbalance and IQ skew, and compensate linear and nonlinear impairments at the same time. We also utilized partial kernel VE to reduce the complexity by retaining part of the 2nd-order kernels.

800-Gb/s/carrier WDM Coherent Transmission Over 2000 km Based on Truncated PS-64QAM Utilizing MIMO Volterra Equalizer

Orthogonal frequency division multiplexing (OFDM) is a promising solution in photonics-aided millimeter-wave (MMW) communication systems, which combine the features of fiber and wireless links. In such a fiber-wireless system, the broadband OFDM signals could be affected by the multipath effect, chromatic dispersion, frequency synchronization error, and other complex impairments. Therefore, both inter-symbol interference (ISI) and inter-carrier interference (ICI) will cause performance degradation. In this experiment, a D-band photonics-aided MMW communication system is demonstrated. To compensate for the linear and nonlinear distortions during the fiber and wireless transmission, we proposed a novel time-frequency domain equalizer based on a two-dimensional convolutional neural network (2D-CNN) with a complex-valued structure. Moreover, a residual branch is adopted. We investigate the bit error rate (BER) performance of the OFDM signals transmission with different modulation formats. With the aid of complex-valued 2D-CNN based equalization, 40 Gbit/s 16QAM and 55 Gbit/s PS-64QAM signals can be successfully transmitted over 200 m wireless distance at the D-band while satisfying the HD-FEC (3.8 × 10−3) and SD-FEC (2.0 × 10−2) threshold, respectively. Moreover, the complex-valued structure can bring significant sensitivity improvements compared to the real-valued 2D-CNN equalization.

Complex-Valued 2D-CNN Equalization for OFDM Signals in a Photonics-Aided MMW Communication System at the D-Band

We experimentally demonstrate 16-GBaud PS-256QAM signal transmission over 104-m wireless distance at 339 GHz in a photonics-aided THz-wave communication system, achieving a record single line rate of 124.8 Gbit/s and net SE of 6.2 bit/s/Hz.

Cuiwei Liu

Papers

640-Gbps/Carrier WDM Transmission over 6,400 km Based on PS-16QAM at 106 Gbaud Employing Advanced DSP

Enhancement of dissolution of cyclosporine A using solid dispersions with polyoxyethylene (40) stearate.

800-Gb/s/carrier WDM Coherent Transmission Over 2000 km Based on Truncated PS-64QAM Utilizing MIMO Volterra Equalizer

Complex-Valued 2D-CNN Equalization for OFDM Signals in a Photonics-Aided MMW Communication System at the D-Band

104-m Terahertz-Wave Wireless Transmission Employing 124.8-Gbit/s PS-256QAM Signal