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Maniruzzaman, M.

Publications and source records attributed to Maniruzzaman, M..

2 recordsLinked to original sources
bioRxiv2021

Selective Laser Sintering of a Photosensitive Drug: Impact of Processing and Formulation Parameters on Degradation, Solid-State, and Quality of 3D Printed Dosage Forms

This research study utilized a light-sensitive drug, nifedipine (NFD), to understand the impact of processing parameters, and formulation composition on drug degradation, crystallinity, and quality attributes (dimensions, hardness, disintegration time) of selective laser sintering (SLS) based 3D printed dosage forms. Selective laser sintering (SLS), in most cases, uses an ultraviolet laser source, and drugs tend to absorb radiation at varying intensities around this wavelength (455 nm). This phenomenon may lead to chemical degradation, and solid-state transformation, which was assessed for nifedipine in formulations with varying amounts of vinyl pyrrolidone-vinyl acetate copolymer (Kollidon(R) VA 64) and potassium aluminum silicate-based pearlescent pigment (Candurin(R)), processed under different SLS conditions in the presented work. After preliminary screening Candurin(R), surface temperature (ST), and laser speed (LS) were identified as the significant independent variables. Further, using the identified independent variables a 17-run, randomized, Box-Behnken design was developed to understand the correlation trends and quantify the impact on degradation (%), crystallinity, quality attributes (dimensions, hardness, disintegration time) employing qualitative and quantitative analytical tools. The design of experiments (DoE) and statistical analysis observed that LS and Candurin(R) (%wt) had a strong negative correlation on drug degradation, hardness, and weight, whereas ST had a strong positive correlation with, drug degradation, amorphous conversion, and hardness of the 3D printed dosage form. From this study, it can be concluded that formulation and processing parameters have a critical impact on stability and performance; hence these parameters should be evaluated and optimized before exposing light-sensitive drugs to the SLS processes. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=126 SRC="FIGDIR/small/439089v1_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@1e3dd02org.highwire.dtl.DTLVardef@c2bfaforg.highwire.dtl.DTLVardef@1b6b712org.highwire.dtl.DTLVardef@ad35fd_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗
bioRxiv2021

Synergistic application of continuous granulation and selective laser sintering 3D printing for the development of pharmaceutical dosage forms with enhanced dissolution rates and physical properties

This study demonstrated the first case of combining novel continuous granulation with powder-based pharmaceutical 3-dimensional (3D) printing processes to enhance the dissolution rate and physical properties of a poorly water-soluble drug. Powder bed fusion (PBF) and binder jetting 3D printing processes have gained much attention in pharmaceutical dosage form manufacturing in recent times. Although powder bed-based 3D printing platforms have been known to face printing and uniformity problems due to the inherent poor flow properties of the pharmaceutical physical mixtures (feedstock). Moreover, techniques such as binder jetting currently do not provide any solubility benefits to active pharmaceutical ingredients (APIs) with poor aqueous solubility (>40% of marketed drugs). For this study, a hot-melt extrusion-based versatile granulation process equipped with UV-Vis process analytical technology (PAT) tools for the in-line monitoring of critical quality attributes (i.e., solid-state) of indomethacin was developed. The collected granules with enhanced flow properties were mixed with vinylpyrrolidone-vinyl acetate copolymer and a conductive excipient for efficient sintering. These mixtures were further characterized for their bulk properties observing an excellent flow and later subjected to a PBF-3D printing process. The physical mixtures, processed granules, and printed tablets were characterized using conventional as well as advanced solid-state characterization. These characterizations revealed the amorphous nature of the drug in the processed granules and printed tablets. Further, the in vitro release testing of the tablets with produced granules as a reference standard depicted a notable solubility advantage (100% drug released in 5 minutes at >pH 6.8) over the pure drug and the physical mixture. Our developed system known as DosePlus combines innovative continuous granulation and PBF-3D printing process which can potentially improve the physical properties of the bulk drug and formulations in comparison to when used in isolation. This process can further find application in continuous manufacturing of granules and additive manufacturing of pharmaceuticals to produce dosage forms with excellent uniformity and solubility advantage. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=119 SRC="FIGDIR/small/430988v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@29c7caorg.highwire.dtl.DTLVardef@fbae3eorg.highwire.dtl.DTLVardef@16c8de1org.highwire.dtl.DTLVardef@1d6b088_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗