Pharmaceutical applications of 3D printing technology: current understanding and future perspectives

Abstract

Three-dimensional printing (3DP) technology allows the fabrication of 3D objects with various geometrics in a layer-by-layer process. Some advantages of 3DP methods over the conventional manufacturing processes include the customization of medicines with individually adjusted doses, the ability to fabricate the sophisticated and complex solid dosage forms, on-demand manufacturing, and cost-effectiveness. Furthermore, recent years have seen an increasing interest in applying 3DP technology to the pharmaceutical manufacturing of drug products and development of various drug delivery systems. However, although 3DP technology exhibits many potential medical and economic benefits, there are also some technical and regulatory challenges restricting the wide applications of 3DP technology to pharmaceutical products. Accordingly, continuous innovation and refinement in 3DP methods are needed to overcome the current limitations and facilitate patient-specific health care with on-demand tailored medications in the future. This review introduces some 3DP techniques suitable for pharmaceutical manufacturing and also their applications to the development of drug dosage forms, indicating the feasibility of this technology in regular commercial production.

Correction to: 10.1007/s40005-018-00414-y, 10.1007/s40005-018-00418-8, 10.1007/s40005-019-00441-3, and 10.1007/s40005-019-00446-y This article is published with open access at Springerlink.com.

Correction to: Poly(lactic acid)/poly(lactic-co-glycolic acid) particulate carriers for pulmonary drug delivery The article poly(lactic acid)/poly(lactic-co-glycolic acid) particulate carriers for pulmonary drug delivery, written by Fakhrossadat Emami, Seyed Jamaleddin Mostafavi Yazdi, and Dong Hee Na, was originally published electronically on the publisher’s internet portal (currently SpringerLink) on 22 April 2019 without open access.

Correction to: Poly(lactic acid)/poly(lactic-co-glycolic acid)-based microparticles: an overview The article Poly(lactic acid)/poly(lactic-co-glycolic acid)-based microparticles: an overview, written by Paolo Blasi, was originally published electronically on the publisher’s internet portal (currently SpringerLink) on 11 June 2019 without open access.

Formulation and statistical analysis of an herbal medicine tablet containing Morus alba leaf extracts Abstract It has reported that Morus alba has properties to treat fever, protect liver damage, improve eyesight, strengthen the joint, facilitate discharge of urine, and prevent high blood pressure. Extracts from herbal plants, have hygroscopic and low flowability characteristics. Due to these properties, it is difficult to develop the formulation using herbal extracts in pharmaceutics. In this study, Morus alba leaf extract (MLE) was fermented by Viscozyme® (MLE-V) and Pectinex® (MLE-P) as well as non-fermented MLE (MLE-C). Physicochemical properties of MLEs were evaluated for optimization of formulation. As a result, cell viability was higher MLE-V than MLE-P, although there was no difference in flowability depending on the enzyme type. Based on the pre-formulation study, MLE-V was selected. Wet granulation method was used to overcome the poor flowability of MLE and MLE tablet was developed by statistical-based experimental design method. A Box-Behnken design, one of the models of experimental design, was constructed using lactose content in lactose plus microcrystalline cellulose (X1), disintegration agent (X2), and binding agent (X3). The dependent variables were hardness (Y1), friability (Y2), and disintegration time (Y3). Finally, MLE tablet with hardness (11.83 ± 0.36 Kp), friability (0.26 ± 0.01%) and disintegration time (1395.56 ± 49.84 s) were optimized. This is the first work to report the formulation design using herbal extracts fermented with enzyme through quality by design.

Casein-based hydrogel carrying insulin: preparation, in vitro evaluation and in vivo assessment Abstract Hydrogels show great potential particularly in the development of drug delivery because of their desirable properties. The enzymatic crosslinked casein hydrogel is a new generation and has received great attention for drug delivery. In the present study, the enzymatic crosslinked casein hydrogel containing insulin was prepared and in vitro and in vivo evaluations were assessed. The hydrogels were also evaluated using differential scanning calorimeter; X-ray diffraction; Scanning electron microscopy and Atomic force microscopy methods. The rheological and releasing behaviors at different media were also investigated. The secondary structure of insulin was assayed by CD method and finally, the hypoglycemic effects were tested in the diabetic rats. Hydrogel showed a three-dimensional porous structure. Rheographs indicated the combination of thixotropic and pseudoplastic behaviors. In vitro release studies confirmed that insulin released in acidic condition slowly, however, in neutral and alkaline environments insulin rapidly released. The structure of insulin preserved following release. Hypoglycemic effects were observed by oral administration of insulin-loaded hydrogel. Thus, the enzymatic crosslinked hydrogel can be considered as a good candidate for oral delivery of insulin.

Characterization of crosslinked hard gelatin capsules for a structural assembly of elementary osmotic pump delivery system Abstract The objective of this study was to characterize the crosslinked hard gelatin capsules (HGCs) for use as a structural assembly of elementary osmotic pumps (EOP). HGCs were crosslinked in formaldehyde vapor for 6, 12, and 24 h. Weight loss after immersing in various mediums, water soluble protein fraction, loss on drying, and formaldehyde residue were investigated. Fourier transform infrared (FTIR) spectra were used to detect the crosslinking formation. The EOP capsules were prepared for delivery of diltiazem hydrochloride (DIL HCl) and ambroxol hydrochloride (AMB HCl), which are freely and sparingly water soluble drugs, respectively. Physicochemical stability of storage crosslinked HGC shells was investigated. All crosslinked HGC shells were water insoluble. FTIR spectra exhibited intermediate lysine methylol and arginine methylol peaks. Storage time increased, moisture content increased and formaldehyde residue decreased. The developing EOP capsules were more appropriate for delivery of high water soluble rather than low water soluble drug. EOP capsule contained 100 mg DIL HCl using HGCs crosslinked for 12 h provided release profiles for 12 h with a lag time of 2.6–3.1 h. It was also found that DIL HCl EOP capsules prepared using crosslinked HGC shells stored for 90 days maintained the similar drug release profiles. AMB HCl EOP capsules exhibited low drug release. In summary, the crosslinked HGCs were applicable as a structural assembly of the osmotic controlled drug delivery system.

Comparison of UPLC-MS/MS and HPLC-UV methods for the determination of zaltoprofen in human plasma Abstract The aim of this study was to compare UPLC-MS/MS and HPLC-UV methods for the determination of zaltoprofen in human plasma. In HPLC-UV, zaltoprofen was separated using 1% (v/v) aqueous acetic acid (pH 2.2) and acetonitrile (ACN) mixed with methanol as a mobile phase (1% aqueous acetic acid/ACN/methanol, 36/60/4, v/v/v) by isocratic elution at a flow rate of 1.0 mL/min with a Zorbax ODS column (250 × 4.6 mm, 5 µm). Quantification of zaltoprofen was performed using a UV detector (330 nm). In UPLC-MS/MS, zaltoprofen was separated using 0.1% (v/v) aqueous formic acid containing 0.5% (v/v) of 10 mM ammonium formate (pH 3.2) buffer (pH 2.3) and ACN as a mobile phase by gradient elution at a flow rate of 0.3 mL/min with a KINETEX core–shell C18 column (50 × 2.1 mm, 1.7 µm). Quantitation of UPLC-MS/MS was performed on a triple quadrupole mass spectrometer using electrospray ionization, operating in the multiple reaction monitoring positive ion mode. The calibration ranges for zaltoprofen in HPLC-UV and UPLC-MS/MS were 0.05–20 and 0.005–10 µg/mL, respectively. The developed methods satisfied the international guidance criteria and can be successfully applied to pharmacokinetic study of an 80 mg zaltoprofen tablet after oral administration to humans.

Microneedle-mediated delivery of cosmeceutically relevant nucleoside and peptides in human skin: challenges and strategies for dermal delivery Abstract Background Highly specific biologically active nucleoside and small peptides, sub fragments of collagen, in specific sequences, have attracted increasing attention for their use in the cosmeceutical field. To be effective in improving the skin and treating skin conditions, it is crucial for these cosmetic ingredients to be delivered through the epidermis and into the viable dermis. Area covered In this review, skin permeation, metabolism and clinical efficacy evaluation studies with microneedle application on adenosine and collagen sub fragments peptides, such as GHK and KTTKS were discussed. Strategies to counteract fragile and rapid clearance of nucleoside and peptides, such as specific peptide derivatives resistant to protease activity, peptide polymer conjugation, polymer encapsulated peptide delivery system incorporated within microneedles, were also discussed. Expert opinion In recent years, various types of microneedle systems such as self-dissolving hyaluronic acid microneedle and pre-treat micro array have been introduced for peptides to traverse the epidermis and into the subcutaneous layer by passive permeation. Microneedle approach can bypass stratum corneum that is a major diffusion barrier to peptides, and has offered a potentially revolutionary advance in cosmeceutical application. However, to support claimed benefits of microneedle application, advanced strategies to counteract degradation of nucleoside and peptides in the skin are required.

Medicinal plants and phytochemicals for diabetes mellitus: pharmacokinetic characteristics and herb-drug interactions Abstract Background Diabetes mellitus (diabetes) is a group of chronic metabolic diseases characterized by high blood sugar levels over a prolonged period, eventually leading to damage of multiple body systems. To date, drug-based therapies have not provided ideal clinical outcomes for effective and safe management of diabetes and its complications. Over the past decade, the use of complementary and alternative medicines (e.g., medicinal herbs and dietary supplements) for the management of chronic diseases such as diabetes has greatly increased around the world. However, herbal medicinal products are complex mixtures of various bioactive constituents that can modulate drug-metabolizing enzymes, particularly cytochrome P450 (CYP), and interact with prescription drugs through pharmacokinetic mechanisms. Area covered Thus, a summary on the effects of antidiabetic herbs and phytochemicals on the pharmacokinetics of antidiabetic drugs may prove relevant for optimizing antidiabetic therapy. The aim of this article is to provide an updated review of the pharmacokinetic characteristics of antidiabetic herbs and phytochemicals and their interactions with conventional antidiabetic drugs. Expert opinion Since herb-drug interactions may lead to substantial pharmacodynamic and/or pharmacokinetic consequences, further research in relevant fields of diabetes and herbal medicine is needed to continuously improve our knowledge of potential risks and benefits associated with these interactions.