Nowadays, the use of marine by-products as precursor materials has gained great interest in the extraction and production of chemical compounds with suitable properties and possible pharmaceutical applications. The present paper presents the development of a new immediate release tablet containing calcium lactate obtained from Black Sea mussel shells. Compared with other calcium salts, calcium lactate has good solubility and bioavailability. In the pharmaceutical preparations, calcium lactate was extensively utilized as a calcium source for preventing and treating calcium deficiencies. The physical and chemical characteristics of synthesized calcium lactate were evaluated using Fourier Transform Infrared Spectroscopy, X-ray diffraction analysis and thermal analysis. Further, the various pharmacotechnical properties of the calcium lactate obtained from mussel shells were determined in comparison with an industrial used direct compressible Calcium lactate DC (PURACAL®). The obtained results suggest that mussel shell by-products are suitable for the development of chemical compounds with potential applications in the pharmaceutical domain.

Captopril is the first angiotensin I-converting enzyme inhibitor widely used for the treatment of hypertension. Based on the well-known benefits of cyclodextrin inclusion complexes, the present study investigated the ability of β-cyclodextrin to include captopril. Solid inclusion complexes of captopril with β–cyclodextrin in a 1:2 molar ratio were prepared by using the paste method of complexation. For comparison purposes, a simple physical mixture with the same molar ratio was also prepared. Fourier-transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction and simultaneous thermal analysis were used to characterize the raw materials, physical mixture and solid inclusion complex. In order to provide the drug in a more accessible and patient-compliant form following masking its bitter taste, as well as ensuring the appropriate release kinetics, the investigated complex was formulated as orally disintegrating tablets. The study of captopril dissolution in both compendial and simulated saliva media suggested the Noyes Whitney model as the best mathematical model to describe the release phenomena. A clinical study on healthy volunteers also highlighted the taste improvement of the new formulation as compared to conventional tablets.

Usnea lichens are known for their beneficial pharmacological effects with potential applications in oral medicine. This study aims to investigate the extract of Usnea barbata (L.) Weber ex F.H. Wigg from the Călimani Mountains in canola oil as an oral pharmaceutical formulation. In the present work, bioadhesive oral films (F-UBO) with U. barbata extract in canola oil (UBO) were formulated, characterized, and evaluated, evidencing their pharmacological potential. The UBO-loaded films were analyzed using standard methods regarding physicochemical and pharmacotechnical characteristics to verify their suitability for topical administration on the oral mucosa. F-UBO suitability confirmation allowed for the investigation of antimicrobial and anticancer potential. The antimicrobial properties against Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27353, Candida albicans ATCC 10231, and Candida parapsilosis ATCC 22019 were evaluated by a resazurin-based 96-well plate microdilution method. The brine shrimp lethality assay (BSL assay) was the animal model cytotoxicity prescreen, followed by flow cytometry analyses on normal blood cells and oral epithelial squamous cell carcinoma CLS-354 cell line, determining cellular apoptosis, caspase-3/7 activity, nuclear condensation and lysosomal activity, oxidative stress, cell cycle, and cell proliferation. The results indicate that a UBO-loaded bioadhesive film’s weight is 63 ± 1.79 mg. It contains 315 µg UBO, has a pH = 6.97 ± 0.01, a disintegration time of 124 ± 3.67 s, and a bioadhesion time of 86 ± 4.12 min, being suitable for topical administration on the oral mucosa. F-UBO showed moderate dose-dependent inhibitory effects on the growth of both bacterial and fungal strains. Moreover, in CLS-354 tumor cells, F-UBO increased oxidative stress, diminished DNA synthesis, and induced cell cycle arrest in G0/G1. All these properties led to considering UBO-loaded bioadhesive oral films as a suitable phytotherapeutic formulation with potential application in oral infections and neoplasia.

Phenolic compounds represent an essential bioactive metabolites group with numerous pharmaceutical applications. Our study aims to identify and quantify phenolic constituents of various liquid and dry extracts of Usnea barbata (L.) Weber ex F.H. Wigg (U. barbata) from Calimani Mountains, Romania, and investigate their bioactivities. The extracts in acetone, 96% ethanol, and water with the same dried lichen/solvent ratio (w/v) were obtained through two conventional techniques: maceration (mUBA, mUBE, and mUBW) and Soxhlet extraction (dUBA, dUBE, and dUBW). High-performance liquid chromatography with diode-array detection (HPLC-DAD) was performed for usnic acid (UA) and different polyphenols quantification. Then, the total phenolic content (TPC) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free-radical scavenging activity (AA) were determined through spectrophotometric methods. Using the disc diffusion method (DDM), the antibacterial activity was evaluated against Gram-positive and Gram-negative bacteria known for their pathogenicity: Staphylococcus aureus (ATCC 25923), Streptococcus pneumoniae (ATCC 49619), Pseudomonas aeruginosa (ATCC 27853), and Klebsiella pneumoniae (ATCC 13883). All extracts contain phenolic compounds expressed as TPC values. Five lichen extracts display various UA contents; this significant metabolite was not detected in dUBW. Six polyphenols from the standards mixture were quantified only in ethanol and water extracts; mUBE has all individual polyphenols, while dUBE shows only two. Three polyphenols were detected in mUBW, but none was found in dUBW. All U. barbata extracts had antiradical activity; however, only ethanol and acetone extracts proved inhibitory activity against P. aeruginosa, S. pneumoniae, and S. aureus. In contrast, K. pneumoniae was strongly resistant (IZD = 0). Data analysis evidenced a high positive correlation between the phenolic constituents and bioactivities of each U. barbata extract. Associating these extracts’ properties with both conventional techniques used for their preparation revealed the extraction conditions’ significant influence on lichen extracts metabolites profiling, with a powerful impact on their pharmacological potential.

The aim of our study was to obtain rutoside (RUT) inclusion complexes in β-cyclodextrin (β-CD) and in hydroxypropyl-β-cyclodextrin (HP-β-CD), in a 1:1 molar ratio, using the lyophilization method of complexation in solution. The complexes were confirmed and characterized, in comparison with the raw materials and their simple physical mixtures, by SEM, DSC, and FT-IR analyses. The antioxidant activity of the compounds was assessed by using the 2,2-diphenyl-1-picryl-hydrazyl (DPPH) and 2’-azino-bis(3-ethylbenzothiazolin-6-sulfonic) acid (ABTS) radicals, determining the radical scavenging activity, and by ferric reducing antioxidant power (FRAP) assay. The results revealed superior antioxidant ability for the inclusion complexes towards rutoside alone. The inclusion complexes were used as active ingredients in formulations of immediate-release tablets. The preformulation studies were performed on the powders for direct compression obtained after mixing the active ingredients with the excipients (Avicel PH 102, Polyplasdone XL-10, magnesium stearate, and talc). The materials were assessed for particle size, flowability, compressibility, and moisture content, establishing they are suitable for a direct compression process. The tablets were characterized regarding their pharmaco-technical properties and the results proved that the formulations lead to high-quality delivery systems, showing a good mechanical resistance with a low friability, excellent disintegration times, and satisfying dissolution rate. The performances were very similar for both formulations and the physico-mechanical properties of the tablets are not influenced by type of the used cyclodextrin, but the RUT- HP-β-CD tablets presented a higher dissolution rate.

Alpha-lipoic acid (ALA, thioctic acid), a naturally-occurring essential dithiol compound, has become a common ingredient in many pharmaceutical and food supplement products (FSP), used in oxidative stress-dependent pathologies; oral bioavailability of ALA is limited by pharmacokinetic particularities that reduce its therapeutic efficacy-reduced solubility, lack of gastric stability and hepatic degradation, doubled by formulation hinders. The objectives were to develop a solid oral 600 mg ALA FSP to obtain an optimal pharmaceutical profile compared to a reference listed drug (RLD) with a similarity factor f2 50. A comparative dissolution study was performed; an HPLC method was used for ALA quantification. After planning combinatory simulations (formulation stage), two prototype formulas (#1 and #2) were manufactured and further optimized by adjusting ALA physical characteristics and the excipients quantities (#3 and #4) in order to achieve the Quality Target Product Profile. A misshapen of ALA’s in vitro release was observed for #3 Formula (f2 = 31.6); the optimal profile was obtained for Formula #4 (f2 = 58.5). A simple quantitative formula is not enough to assure good ALA bioavailability; the formulation needs multiple compounding modulations under physicochemical compatibility algorithms, with multiple dissolution profiles testing back-ups. It is essential to ensure a formulation with an in vitro dissolution comparable with the RLD, allowing the compound to reach its target level to assure the optimum claimed antioxidant activity of ALA at the cellular level, even for food supplement formulations.

Oral squamous cell carcinoma (OSCC) is the most frequent oral malignancy, with a high death rate and an inadequate response to conventional chemotherapeutic drugs. Medical research explores plant extracts’ properties to obtain potential nanomaterial-based anticancer drugs. The present study aims to formulate, develop, and characterize mucoadhesive oral films loaded with Usnea barbata (L.) dry acetone extract (F-UBA) and to investigate their anticancer potential for possible use in oral cancer therapy. U. barbata dry acetone extract (UBA) was solubilized in ethanol: isopropanol mixture and loaded in a formulation containing hydroxypropyl methylcellulose (HPMC) K100 and polyethylene glycol 400 (PEG 400). The UBA influence on the F-UBA pharmaceutical characteristics was evidenced compared with the references, i.e., mucoadhesive oral films containing suitable excipients but no active ingredient loaded. Both films were subjected to a complex analysis using standard methods to evaluate their suitability for topical administration on the oral mucosa. Physico-chemical and structural characterization was achieved by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and atomic force microscopy (AFM). Pharmacotechnical evaluation (consisting of the measurement of specific parameters: weight uniformity, thickness, folding endurance, tensile strength, elongation, moisture content, pH, disintegration time, swelling rate, and ex vivo mucoadhesion time) proved that F-UBAs are suitable for oral mucosal administration. The brine shrimp lethality (BSL) assay was the F-UBA cytotoxicity prescreen. Cellular oxidative stress, caspase 3/7 activity, nuclear condensation, lysosomal activity, and DNA synthesis induced by F-UBA in blood cell cultures and oral epithelial squamous cell carcinoma (CLS-354) cell line were investigated through complex flow cytometry analyses. Moreover, F-UBA influence on both cell type division and proliferation was determined. Finally, using the resazurin-based 96-well plate microdilution method, the F-UBA antimicrobial potential was explored against Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27353, Candida albicans ATCC 10231, and Candida parapsilosis ATCC 22019. The results revealed that each UBA-loaded film contains 175 µg dry extract with a usnic acid (UA) content of 42.32 µg. F-UBAs are very thin (0.060 ± 0.002 mm), report a neutral pH (7.01 ± 0.01), a disintegration time of 146 ± 5.09 s, and an ex vivo mucoadhesion time of 85 ± 2.33 min, and they show a swelling ratio after 6 h of 211 ± 4.31%. They are suitable for topical administration on the oral mucosa. Like UA, they act on CLS-354 tumor cells, considerably increasing cellular oxidative stress, nuclear condensation, and autophagy and inducing cell cycle arrest in G0/G1. The F-UBAs inhibited the bacterial and fungal strains in a dose-dependent manner; they showed similar effects on both Candida sp. and higher inhibitory activity against P. aeruginosa than S. aureus. All these properties lead to considering the UBA-loaded mucoadhesive oral films suitable for potential application as a complementary therapy in OSCC.

Due to its low solubility, carbamazepine (CBZ) exhibits slow and incomplete release in the gastrointestinal tract and, hence, variable pharmacokinetics and pharmacodynamic effect. Lots of methods have been devised to improve its solubility, the large number of proposed solutions being a sign that the problem is not yet satisfactorily solved. The persistent problem is that predictable release kinetics, an increased rate but within defined limits, are required to avoid high absorption variability. This paper presents a synthesis of a carbamazepine-β-cyclodextrin inclusion complex (CBZ-β-CD), the characterization of the physical mixture, CBZ, β-CD and the CBZ-β-CD inclusion complex using Fourier transform infrared spectroscopy, scanning electron microscopy, simultaneous thermal analysis and X-ray diffraction, formulation of chewable tablets, determination of the dissolution of carbamazepine in medium containing 1% sodium lauryl sulfate (LSS), and in simulated saliva (SS), mathematical modeling of release kinetics. The kinetics of total CBZ release from tablets containing CBZ-β-CD and super-disintegrant F-Melt in both SS and LSS followed two steps: a burst release in the first minutes and a slower release in intervals up to 60 min. The release in the second phase has been well described by the Higuchi and Peppas models, which advocate a controlled release by combined diffusion and with some phenomena of swelling and relaxation of the matrix generated by the crospovidone component of the F-Melt excipient.