Journal of Pharmaceutical and BioTech Industry

A selective inhibitor of cyclooxygenase-2 (COX-2), Celecoxib (CEB), known for its anti-inflammatory properties, can exhibit polymorphism, with Form III often emerging as an undesired crystalline impurity during the green manufacturing process of the preferred Form I. Controlling the Form III content in the drug product is crucial, as different crystalline forms can impact drug bioavailability and therapeutic efficacy. This study presents a method to quantify the weight percentage of Form III in the bulk of CEB Form I by employing powder X-ray diffraction (PXRD). Initially, pure Form I and III of CEB were characterized using DSC, FTIR, and PXRD, supporting the method’s development. Binary mixtures, with varying ratios of CEB polymorphs Form I and Form III, were prepared and analyzed using continuous scans over an angular (2θ) range of 2–40. The calibration curve was constructed using 2θ unique peaks for Form I and Form III, respectively. Linear regression analysis exhibited a strong linear relationship within the weight ratio range of 1–20%. The developed method was validated to assess recovery, precision, ruggedness, limits of detection, and quantitation. These findings indicate that the method exhibits repeatability, sensitivity, and accuracy. The newly developed and validated PXRD method is applicable for quality control of CEB Form I produced through the green melt crystallization process by detecting low levels of Form III polymorphic impurity. This research significantly contributes to ensuring the clinical efficacy and manufacturing quality of Celecoxib by providing a reliable method for controlling polymorphic impurities. Full article

Lidocaine plays a significant role in postoperative analgesia by effectively reducing pain. However, due to its short half-life, it is challenging for lidocaine to achieve the desired duration of analgesia in clinical settings. Drug delivery systems can regulate the release rate over time, making them one of the most effective strategies for achieving sustained release. In this work, a multi-level drug delivery system was designed using hyaluronic acid-modified zeolitic imidazolate framework-8 (HA/ZIF-8) nanoparticles and injectable hydrogels composed of modified natural polymers. Lidocaine was incorporating into the modified ZIF-8 and uniformly dispersed within the hydrogel network. The dynamic light scattering (DLS) and Fourier transform infrared spectrometer (FTIR) results indicate the successful loading of lidocaine into ZIF-8, while the X-ray diffractometer (XRD) results confirm that the loading of lidocaine did not disrupt the crystal structure of ZIF-8. The coating of hyaluronic acid on ZIF-8 enhanced cell biocompatibility, with cell viability increasing by 89% at the same concentration. This multi-level drug delivery system can be injected through a 27-guage needle. In vitro release studies demonstrated a sustained release of lidocaine for more than 4 days and kinetic simulations aligned with the Bshakar model, indicating its potential for use in long-acting analgesic preparations. Full article

Lyophilization, or freeze-drying, is the default technique for the manufacture of solid-state formulations of therapeutic proteins. This established method offers several advantages, including improved product stability by minimizing chemical degradation, reduced storage requirements through water removal, and elimination of cold chain dependence. However, the lyophilization process itself presents limitations. It is a lengthy, batch-based operation, potentially leading to product inconsistencies and high manufacturing costs. Additionally, some proteins are susceptible to structural alterations during the freezing step, impacting their biological activity. This paper presents an alternative approach based on the co-precipitation of protein and excipients using an organic solvent. We explore the impact of various processing parameters on the viability of the formulation. We also provide an extensive characterization of proteins reconstituted from precipitated formulations and compare protein stability in solution and in lyophilized and precipitated solid formulations under long-term, accelerated, and stressed storage conditions. Full article

Poor solubility of many drugs, with ensuing low bioavailability, is a big challenge in pharmaceutical development. Nanosuspensions have emerged as a platform approach for long-acting injectables and solid dosages that enhance drug bioavailability. Despite improvements in nanosuspension preparation methods, ensuring nanosuspension stability remains a critical issue. Conventionally, synthetic and semi-synthetic polymers and surfactants are used in nanosuspension formulations. However, no polymer or surfactant group is universally applicable to all drugs. This fact, as well as their toxicity and side effects, especially if used in excess, have sparked the interest of researchers in the search for novel, natural stabilizers. The objective of this paper is to provide a comprehensive analysis of non-traditional natural stabilizers reported in the literature published over the last decade. First, physical stability and stabilization mechanisms are briefly reviewed. Then, various classes of non-traditional natural stabilizers are introduced, with particular emphasis on their stabilization potential, safety, and pharmaceutical acceptability. Wherever data were available, their performance was compared with the traditional stabilizers. Furthermore, the benefits and limitations of using these stabilizers are examined, concluding with future prospects. This review is expected to serve as a valuable guide for researchers and formulators, offering insights into non-traditional natural stabilizers in drug nanosuspension formulations. Full article

Celecoxib (CEL), a nonsteroidal anti-inflammation drug (NSAID), is categorized as a Class II drug (low solubility, high permeability) in the Biopharmaceutics Classification System (BCS). The aim of this study is to develop a novel formulation of CEL nanosuspensions in the form of dried powder for tableting or capsuling. In this study, CEL was formulated into nanosuspensions to improve its solubility. CEL nanosuspensions were prepared using the precipitation method followed by high-pressure homogenization. Drying of the nanosuspensions was performed by spray drying and freeze drying. We examined the impact of various formulation and processing parameters on the nanoparticles. The CEL nanoparticles were characterized by particle size analysis, differential scanning calorimetry (DSC), powder X-Ray diffraction (PXRD), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), and dissolution tests. The choice of solvent, stabilizer, and surfactant appeared to have significant impacts on the crystallization and particle size and, consequently, the solubility of the CEL nanoparticles. CEL chemical stability was maintained throughout both drying processes. Both spray-dried and freeze-dried CEL nanosuspensions showed rapid dissolution profiles compared to raw CEL due to the nanosized particle dispersion with the presence of a lag phase. The freeze-dried nanosuspension showed a slight delay in the first 20 min compared to the spray-dried nanosuspension, after which dissolution progressed with a lag phase that represents aggregation. Full article

Background: The aqueous solubility of indomethacin, a poorly water-soluble anti-inflammatory drug, was enhanced by co-crystallization with co-formers. The co-crystals were characterized and compared by an X-ray diffraction (XRD) analysis, terahertz (THz) spectroscopy, and Fourier transform infrared (FT-IR) spectroscopy. Methods: Indomethacin co-crystals with either amides (saccharin, nicotine amide, and urea) or amino acids (lysine and histidine) as co-formers were prepared through the solvent evaporation method. The co-crystals were characterized by XRD, THz, and FT-IR analyses, followed by solubility tests to examine the solubility enhancement. Results: Both the XRD and THz analyses were capable of distinguishing co-crystals from physical mixtures; however, the THz spectra were relatively simpler and clearer than the XRD analysis. Furthermore, the solubility of indomethacin was successfully increased by two to three times that of pure indomethacin after co-crystallization with the above five co-formers. Conclusion: Five kinds of indomethacin co-crystals (with enhanced solubility) were successfully prepared and confirmed by the three spectroscopy techniques, XRD, THz, and FT-IR. The identification of co-crystals was achieved by a THz analysis, giving relatively simpler and clearer spectra with less noise. Hence, in addition to an XRD analysis, a THz analysis (a non-destructive, non-ionizing radiative, and relatively rapid measurement technique which is convenient and safe to use) is a good alternative method to characterize co-crystals. Full article