Background: Pharmaceutical co-crystals are the homogeneous crystalline substances composed of two or more substances bound together in the same crystal lattice via noncovalent interactions like hydrogenbonding, electrostatic interaction and Vander Waals interactions. Currently, co-crystals provide excellent opportunities to the formulation scientists in developing new pharmaceutical products by improving the pharmaceutically significant properties like solubility, dissolution rate, bioavailability, stability, and some other derived properties. Due to their ability to improve pharmacokinetic performance and their important intellectual property status, co-crystals are likely to have a very significant role in future drug development. Thus, formulation scientists have their focus on the development aspects of a co-crystallization process that include a rational selection of co-former, the discovery of novel synthetic procedures and new characterization techniques, and large scale production of these novel materials. Objective: The objective of this article is to present an extensive review of solvent-free methods for co-crystal synthesis, mainly focusing on the principle mechanisms, advantages, and drawbacks of each method. Conclusion: From the review of the topic, it is clear that the solvent-free methods can offer numerous advantages over solvent-based methods in the design and the production of co-crystals of pharmaceutical use and these methodologies can also pave the path to advancing the field of co-crystal synthesis. Some of the advantages accompanied with solvent-free methods are the use of no or very less amount of solvent(s), exceptional purity and quality of produced co-crystal, large scale production and the short reaction times in few cases.
Background: Curcumin (Curcuma longa) and propranolol display a plethora of pharmacological activity linked with multifunctional druggable nature designated as a promiscuous or dirty drug (magic shotguns) that hit 'on-target as well as 'off-target' (anti-target). Multifactorial origins, with complex neuronal networks and broad-spectrum symptomatology, operates most CNS disorders. Anxiety is one of the comorbidities in the psychogenic spectrum of obsessive-compulsive disorder (OCD). The present study of OCD has been based on its multifunctionality and diverse drug potential, tailoring together the morbidity and comorbidity patterns of OCD. Very few multimodal drugs did trial in this regard, which has multifunctional druggability, except selective serotonin reuptake inhibitors (SSRIs) that work via the one-drug-one-receptor-one-disease approach; however, with inter-individual variability, unwanted side effects and limited multifunctionality with the druggable targets. SSRI success rates in OCD and its related disorder are minimal, especially in the adversity of comorbidity pattern. Objective: The principal objective of the current research was to testify the multifunctional druggable plethora of curcumin via repurposing of its dirty drug nature to reverse the obsessed anxiety of propranolol withdrawal-induce mice, besides the "one drug one receptor" approach or magic bullet. Methods: The present study evaluated OCD related anxiety-like behavior after different periods of abstinence (24 h, 7 and 21 days) from repeated propranolol (10 mg/kg) administration in mice. In addition, we also examined the action of curcumin (EERCL-50 mg/kg) and fluoxetine (20 mg/kg) for the attenuation or reversal of OCD related anxiety-like behavior after seven days to 24 hours propranolol withdrawal. The initial stage of the hypothesis toward the target of curcumin was identified via in-silico using SwissADME drug-likeness study, followed by in-vivo studies using Swiss albino mice. Evaluation for the same did use elevated plus maze (EPM), marble-burying behaviour (MBB) and motor activity (MA) test as a model. Further, did also investigate the antioxidant activity. Result: The result revealed a decrease in all parameters 24 hours and 14 days after exposure to propranolol, indicating anxious behaviour. The administration of curcumin and fluoxetine after 24 hrs of abstinence reduced animal anxiety in EPM; after the abstinence periods, the drug reduced the MA in the MBB. Curcumin reversed the anxiogenic effect induced by propranolol in EPM. The value of p<0.05 was considered statistically significant. Conclusion: Results revealed that propranolol might, to a large extent, impart to withdrawal-induced obsessed anxiety, and curcumin could effectively treat propranolol dependent obsessed mice. Further, curcumin anti-compulsive competency substantially showed promising success besides one drug-one receptor-one disease approach or magic bullet.
The Herbal or natural excipients have great merit over their synthetic analogs as these are non-toxic, low-cost, and freely obtainable. The performance of the excipients partly determines the quality of the medicines. The plant acquired gums, mucilage from the natural origin for example carrageenan, thaumatin, lard, storax, agar, gum acacia, tragacanth, and excipients. They can also be easily altered to meet the specific needs, thereby being a potent many more to name comply with many requirements of the pharmaceutical and economic vehicle for transporting active pharmaceutical ingredients in the formulation. Thus present study aims to throw light on the probable of natural excipients which can be present to be used as a diluent, binder, disintegrant as well as lubricant in different types of formulations as they are biocompatible and capable of giving additional nutrition to the developed dosage form. This article gives an overview of natural excipients which are used in conventional dosage forms as well as novel drug delivery systems.
Protein and peptide are last three decades therapeutic peptides and proteins have risen in prominence as potential drug of future. Polymers of protein consist of amino acids covalently linked by peptide bonds. Peptides are small proteins composed of up to a couple of dozen amino acids proteins are rapidly degraded by digestive enzymes. Till recently, injections remain the foremost common means for administering these protein and peptide drugs. In the other routes that have been tried with varying degrees of success are the oral, buccal, intranasal, pulmonary, transdermal, ocular and rectal. In this review, the aim is to specialise in the varied routes and approaches for delivery of Peptide and protein drugs. The Continuous efforts are focussed for formulation of this therapeutics into safe and effective delivery systems. In this review briefly describes the possible methods for the delivery of protein and peptide drugs through various routes.
Aim: Present research work focuses on the improvement of biopharmaceutical properties of aceclofenac (ACF) by the cocrystal approach.\ Background: ACF is one of the frequently used Nonsteroidal Anti-Inflammatory Drug (NSAID). ACF is a BCS Class - II drug (low solubility and high permeability) with poor solubility and low oral bioavailability. Hence, the improvement in solubility and bioavailability of ACF is very crucial for successful product development. Now a day’s pharmaceutical cocrystals are considered a novel solid form of drugs. These cocrystals may have different physicochemical as well as biopharmaceutical properties as compared to the parent drug. In a previous study, the cocrystal of ACF (ACF-l-CYS NG and ACF-UREA NG) were successfully prepared and characterized. These cocrystals have shown superior solubility and dissolution rate than pure ACF in HCl buffer (pH 1.2). The synthesized cocrystals were also found non-hygroscopic and stable for 6 months under standard test settings. However pharmacokinetic evaluation of these cocrystals have not been explored yet. Objective: The specific objective of this research work was the measurement of bioavailability and other pharmacokinetic parameters of ACF cocrystals prepared by the mechanochemical grinding method. Methods: Cocrystals of ACF with l-cystine and urea were prepared by neat grinding (NG) method and in-vivo oral bioavailability of prepared cocrystals was measured in Wistar rats. The plasma drug concentration was measured by high-performance liquid chromatography (HPLC) and the pharmacokinetic data was analyzed by “PK solver” software. Results : Percent relative bioavailability of ACF-l-CYS NG and ACF-UREA NG cocrystals in Wistar rats was found to be 242.05 ± 65.27and 178.93 ± 45.21 respectively, which were significantly higher (ANOVA, P < 0.05) than that of pure ACF. Conclusion: The present study indicates that the enhanced aqueous solubility of the prepared cocrystals leads to enhanced oral bioavailability of ACF. Thus, the cocrystals may be an alternative crystalline form of the drug that can enhance the solubility, dissolution rate, and oral bioavailability of many poorly soluble drugs.
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