Poly(lactic-co-glycolic acid) (PLGA) has garnered increasing attention as a candidate drug delivery polymer owing to its favorable properties, including its excellent biocompatibility, biodegradability, nontoxicity, non-immunogenicity, and mechanical strength. PLAG are specifically used as microspheres for the sustained/controlled and targeted delivery of hydrophilic or hydrophobic drugs, as well as biological therapeutic macromolecules, including peptide and protein drugs. PLGAs with different molecular weights, lactic acid (LA)/glycolic acid (GA) ratios, and end groups exhibit unique release characteristics, which is beneficial for obtaining diverse therapeutic effects. This review aims to analyze the composition of PLGA microspheres, and understand the manufacturing process involved in their production, from a quality by design perspective. Additionally, the key factors affecting PLGA microsphere development are explored as well as the principles involved in the synthesis and degradation of PLGA and its interaction with active drugs. Further, the effects elicited by microcosmic conditions on PLGA macroscopic properties, are analyzed. These conditions include variations in the organic phase (organic solvent, PLGA, and drug concentration), continuous phase (emulsifying ability), emulsifying stage (organic phase and continuous phase interaction, homogenization parameters), and solidification process (relationship between solvent volatilization rate and curing conditions). The challenges in achieving consistency between batches during manufacturing are addressed, and continuous production is discussed as a potential solution. Finally, potential critical quality attributes are introduced, which may facilitate the optimization of process parameters.

In recent years, nanocrystal technology has been extensively investigated. Due to the submicron particle size and unique physicochemical properties of nanocrystals, they overcome the problems of low drug solubility and poor bioavailability. Although the structures of nanocrystals are simple, the further development of these materials is hindered by their stability. Drug nanocrystals with particle sizes of 1∼1000 nm usually require the addition of stabilizers such as polymers or surfactants to enhance their stability. The stability of nanocrystal suspensions and the redispersibility of solid nanocrystal drugs are the key factors for the large-scale production of nanocrystal preparations. In this paper, the factors that affect the stability of drug nanocrystal preparations are discussed, and related methods for solving the stability problem are put forward.

Purpose Proper taste-masking formulation design is a critical issue for instant-dissolving tablets (IDTs). The purpose of this study is to use the electronic tongue to design the additives of the 3D printed IDTs to improve palatability. Methods A binder jet 3D printer was used to prepare IDTs of levetiracetam. A texture analyzer and dissolution apparatus were used to predict the oral dispersion time and in vitro drug release of IDTs, respectively. The palatability of different formulations was investigated using the ASTREE electronic tongue in combination with the design of experiment and a model for masking bitter taste. Human gustatory sensation tests were conducted to further evaluate the credibility of the results. Results The 3D printed tablets exhibited rapid dispersion (<30 s) and drug release (2.5 min > 90%). The electronic tongue had an excellent ability of taste discrimination, and levetiracetam had a good linear sensing performance based on a partial least square regression analysis. The principal component analysis was used to analyze the signal intensities of different formulations and showed that 2% sucralose and 0.5% spearmint flavoring masked the bitterness well and resembled the taste of corresponding placebo. The results of human gustatory sensation test were consistent with the trend of the electronic tongue evaluation. Conclusions Owing to its objectivity and reproducibility, this technique is suitable for the design and evaluation of palatability in 3D printed IDT development.

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Azithromycin (AZI) is one of the most commonly used macrolide antibiotics in children, but has the disadvantages of a heavy bitter taste and poor solubility. In order to solve these problems, hot-melt extrusion (HME) was used to prepare azithromycin amorphous solid dispersion. Preliminary selection of a polymer for HME was conducted by calculating Hansen solubility parameter to predict the miscibility of the drug and polymer. Eudragit® RL PO was chosen as the polymer due to its combination of taste-masking effect and dissolution. Moreover, the solubility was improved with this polymer. Design of experiments (DoE) was used to optimize the formulation and process, with screw speed, extrusion temperature, and drug percentage as independent variables, and content, dissolution, and extrudates diameter as dependent variables. The optimal extrusion parameters were obtained as follows: temperature—150 °C; screw speed—75 rpm; and drug percentage—25%. Differential scanning calorimetry (DSC) and Powder X-ray Diffraction (PXRD) studies of the powdered solid dispersions showed that the crystalline AZI transformed into the amorphous form. Fourier transform infrared spectroscopy (FTIR) results indicated that the formation of a hydrogen bond between AZI and the polymer led to the stabilization of AZI in its amorphous form. In conclusion, this work illustrated the importance of HME for the preparation of amorphous solid dispersion of AZI, which can solve the problems of bitterness and low solubility. It is also of great significance for the development of compliant pediatric AZI preparation.