ABSTRACT
Famotidine (FMT) an anti-ulcer drug, recently being repurposed in COVID-19 treatment, suffers from poor aqueous solubility and restricted bioavailability (<40%). To conquer the limitations endured by this potent anti-ulcer agent, two novel 1:1 cocrystals of FMT, namely Famotidine-Sorbic Acid (FSOR) and Famotidine-Syringic Acid (FSY), were synthesized using the liquid-assisted grinding method and evaluated. Distinct DSC thermograms and PXRD patterns advocate the existence of a new crystalline form. The unique organization of the hydrogen-bonded network, in the prepared cocrystals, is inferred by variation in characteristic vibrational frequencies in FT-IR spectroscopic analysis and supported by crystal structure determination. FSOR cocrystallize in orthorhombic PNCB and FSY in triclinic P 1 crystal system. Further, a significant amplification in the solubility (9 to 5-fold) and dissolution (8 to 5-fold) of FMT in cocrystalline form, with simultaneous augmentation in peak plasma concentration (2 to 1.5-fold higher) and relative bioavailability (approx. 200% to 135%). This is associated with the remarkable increment in their anti-ulcer and anti-oxidant potential. Thus, the study illustrates that cocrystallization as a worthy approach in the efficient delivery of neutral compounds suffering from inadequate solubility crisis.
Subject(s)
Anti-Ulcer Agents , Biological Products , COVID-19 Drug Treatment , Antioxidants , Crystallization/methods , Famotidine , Humans , Hydrogen , Pharmaceutical Preparations , Solubility , Sorbic Acid , Spectroscopy, Fourier Transform InfraredABSTRACT
PURPOSE: Rebamipide (REB) a potent anti-ulcer agent, has not been exploited to its full potential, owing to it extremely poor solubility, leading to highly diminutive bioavailability (<10%). The purpose is to carry out its solid-state modification. METHOD: Cocrystallisation was done with three GRAS coformers namely citric acid (CA), 3,4-dihydroxybenzoic acid (DHBA) and oxalic acid (OXA) employing the liquid-assisted grinding method. Cocrystal formation was based upon amide-carboxyl and amide-hydroxyl supramolecular synthons. Characterization of novel cocrystals i.e. RCA, RDHBA and ROXA was carried out by DSC, PXRD and additionally by FT-IR spectroscopy. Chemical structures have been determined utilizing the PXRD pattern by Material Studio®. Furthermore, cocrystals were subjected to solubility and intrinsic dissolution rate (IDR) evaluation. Also, pharmacodynamic and pharmacokinetic studies were performed and compared with pure rebamipide. RESULT: The appearances of a single sharp melting endotherm in DSC, along with novel characteristic peaks in PXRD infer the existence of a new crystalline form. Shifting in characteristic vibrations in FT-IR spectroscopy supports the establishment of distinct hydrogen-bonded networks. Structural determination revealed that RCA crystallizes in 'Bb2b' space groups whereas RDHBA in 'P1' and ROXA crystallize out in the 'P-1' space group. All the cocrystals exhibited superior apparent solubility and almost 7-13 folds increase in IDR. Furthermore, 1.6-2.5 folds enhancement in relative bioavailability and remarkable amplification in anti-ulcer, anti-inflammatory and the antioxidant potential of these cocrystals were observed. CONCLUSION: The study ascertains the advantages of cocrystallization, with RCA showing greatest potential and suggests a viable alternative approach for improved formulation of rebamipide.
Subject(s)
Alanine/analogs & derivatives , Biological Products/chemistry , Chemical Engineering , Edema/drug therapy , Quinolones/chemistry , Stomach Ulcer/drug therapy , Alanine/administration & dosage , Alanine/chemistry , Alanine/pharmacokinetics , Animals , Biological Availability , Biological Products/pharmacokinetics , Carrageenan/administration & dosage , Carrageenan/immunology , Chemistry, Pharmaceutical/methods , Crystallization , Disease Models, Animal , Drug Compounding/methods , Edema/chemically induced , Edema/immunology , Humans , Hydrogen Bonding , Indomethacin , Male , Powder Diffraction , Quinolones/administration & dosage , Quinolones/pharmacokinetics , Rats , Spectroscopy, Fourier Transform Infrared , Stomach Ulcer/chemically inducedABSTRACT
The significance of herbals and herbal products is gaining worldwide recognition. The concept of complementary or alternative medicine is becoming much more widely accepted, and there is an increasing belief in the efficacy of herbal remedies. Recently, the role of herbal drugs, herbal products and certain phytochemicals in the control of ageing has been documented using modern scientific approaches. This review pulls together such studies and critiques the efficacy and value of herbal medicines in the control of the ageing process.
Subject(s)
Aging/drug effects , Cellular Senescence/drug effects , Complementary Therapies , Plant Preparations/pharmacology , Animals , Humans , Molecular Structure , Plant Preparations/chemistry , Structure-Activity RelationshipABSTRACT
Although ageing is a natural wear and tear phenomenon, it can at least be postponed or prevented by certain approaches. Some chemicals that are present in the diet or in dietary supplements have been documented to have anti-ageing effects. Recently, a number of synthetic drugs used for other therapeutic indications have been shown to have anti-ageing potential.
