Recent advancements to enhance the therapeutic efficacy of antiepileptic drugs.

Epilepsy is a multifactorial neurological disorder characterized by recurrent or unprovoked seizures. Over the past two decades, many new antiepileptic drugs (AEDs) were developed and are in use for the treatment of epilepsy. However, drug resistance, drug-drug interaction and adverse events are common problems associated with AEDs. Antiepileptic drugs must be used only if the ratio of efficacy, safety, and tolerability of treatment are favorable and outweigh the disadvantages including treatment costs. The application of novel drug delivery techniques could enhance the efficacy and reduce the toxicity of AEDs. These novel techniques aim to deliver an optimal concentration of the drug more specifically to the seizure focus or foci in the CNS without numerous side-effects. The purpose of this article is to review the recent advancements in antiepileptic treatment and summarize the novel modalities in the route of administration and drug delivery, including gene therapy, for effective treatment of epilepsy.

Potential of amentoflavone with antiviral properties in COVID-19 treatment.

Amentoflavone is one of the flavonoids that are known for their antiviral effects and many of them are predicted to have inhibitory effects against severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome Coronavirus (MERS-CoV) enzymes 3-chymotrypsin-like protease (3CLpro) and papain-like protease (PLpro). Amentoflavone is a biflavonoid found in the herbal extracts of St. John's wort (Hypericum perforatum), Gingko biloba, Selaginella tamariscina, Torreya nucifera, and many other plants. Its pharmacological actions have been listed as antiviral, antibacterial, antioxidant, anti-inflammatory, antidiabetic, antidepressant, and neuroprotective. Molecular docking studies have found that amentoflavone binds strongly to the active site of the main protease (Mpro) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). As conventional antiviral medications are met with limited success against coronavirus disease-2019 (COVID-19) and vaccines are one of the only weapons against COVID-19 in the pharmaceutical armamentarium, traditional medicines are being considered for the forefront battle against COVID-19. Clinical studies with Hypericum and Gingko extract as additional or alternative drugs/supplements are registered. Here we review the potential of amentoflavone, an active agent in both Hypericum and Gingko extract as an adjunct therapy for COVID-19. Its anti-inflammatory, antioxidant, and sepsis preventive actions could provide protection against the "cytokine storm." Compared with the herbal extracts, which induce cytochrome P450 (CYP) and uridine 5'-diphospho (UDP)-glucuronosyltransferases (UGT) activity producing a negative herb-drug interaction, amentoflavone is a potent inhibitor of CYP3A4, CYP2C9, and UGT. Further studies into the therapeutic potential of amentoflavone against the coronavirus infection are warranted.

Synthesis and characterization of pectin-chitosan conjugate for biomedical application.

BACKGROUND: Polysaccharides are extensively used in drug delivery systems due to their ability to undergo a broad range of chemical and enzymatic reactions, forming new molecules. Among these, chitosan (CS) and pectin (PEC) are widely used for designing new conjugates and biopolymers. METHODS: In this study, we synthesized pectin-chitosan conjugate (PEC-CS) by using carbodiimide crosslinking chemistry. Pectin-N-hydroxysuccinimide ester, formed in the presence of dicyclohexylcarbodiimide under anhydrous conditions, was conjugated with chitosan by linking the free carboxyl group of PEC with the primary amino group of chitosan. RESULTS: Fourier-transform infrared spectroscopy confirmed the formation of the PEC-CS conjugate. X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, and scanning electron microscopy analyses showed that the PEC-CS conjugate is amorphous in nature, has high thermostability than those of native polymers, and has no cytotoxicity. CONCLUSION: Our results indicated that PEC-CS conjugate can be further developed for use in drug delivery systems.

Evaluation of chemically modified hydrophobic sago starch as a carrier for controlled drug delivery.

The present investigation deals with the development of controlled release tablets of lamivudine using acetylated sago starch. The acetylated starch was synthesized with acetic anhydride in pyridine medium. The acetylated sago starch was tested for acute toxicity and drug-excipient compatibility study. The formulations were evaluated for physical characteristics like hardness, % friability, % drug content and weight variations. The in vitro release study showed that the optimized formulation exhibited highest correlation (R) value in the case of higuchi kinetic model and the release mechanism study proved that the formulation showed a combination of diffusion and erosion processes. There was a significant difference in the pharmacokinetic parameters (T max, C max, AUC, V d, T 1/2 and MDT) of the optimized formulation as compared to the marketed conventional tablet Lamivir® which proves the controlled release property of acetylated sago starch.

Evaluation of microwave assisted grafted sago starch as controlled release polymeric carrier.

In the present investigation an attempt has been made to develop a new co-polymeric material for controlled release tablet formulations. The acrylamide grafting was successfully performed on the backbone of sago starch. The modified starch was tested for acute toxicity and drug-excipient compatibility study. The grafted material was used in making of controlled release tablets of lamivudine. The formulations were evaluated for physical characteristics such as hardness, friability, %drug content and weight variations. The in vitro release study showed that the optimized formulation exhibited highest correlation (R) value in case of Higuchi model and the release mechanism of the optimized formulation predominantly exhibited combination of diffusion and erosion process. There was a significant difference in the pharmacokinetic parameters (T(max), C(max), AUC, V(d), T(1/2) and MDT) of the optimized formulation as compared to the marketed conventional tablet Lamivir(®) was observed. The pharmacokinetics parameters were showed controlled pattern and better bioavailability. The optimized formulation exhibited good stability and release profile at the accelerated stability conditions.

Formulation development and evaluation of lamivudine controlled release tablets using cross-linked sago starch.

OBJECTIVES: Modified starches based polymeric substances find utmost applicability in pharmaceutical formulation development. Cross-linked starches showed very promising results in drug delivery application. The present investigation concerns with the development of controlled release tablets of lamivudine using cross-linked sago starch. METHODS: The cross-linked derivative was synthesized with phosphorous oxychloride and native sago starch in basic pH medium. The cross-linked sago starch was tested for acute toxicity and drug-excipient compatibility study. The formulated tablets were evaluated for various physical characteristics, in vitro dissolution release study and in vivo pharmacokinetic study in rabbit model. RESULTS: In vitro release study showed that the optimized formulation exhibited highest correlation (R) in case of zero order kinetic model and the release mechanism followed a combination of diffusion and erosion process. There was a significant difference in the pharmacokinetic parameters (T(max), C(max), AUC, V(d), T(1/2), and MDT) of the optimized formulation as compared to the marketed conventional tablet Lamivir®. CONCLUSION: The cross-linked starch showed promising results in terms of controlling the release behavior of the active drug from the matrix. The hydrophilic matrix synthesized by cross-linking could be used with a variety of active pharmaceutical ingredients for making their controlled/sustained release formulations.

Development and validation of analytical method for the estimation of nateglinide in rabbit plasma.

Nateglinide has been widely used in the treatment of type-2 diabetics as an insulin secretogoga. A reliable, rapid, simple and sensitive reversed-phase high performance liquid chromatography (RP-HPLC) method was developed and validated for determination of nateglinide in rabbit plasma. The method was developed on Hypersil BDSC-18 column (250 mm×4.6 mm, 5 mm) using a mobile phase of 10 mM phosphate buffer (pH 2.5) and acetonitrile (35:65, v/v). The elute was monitored with the UV-vis detector at 210 nm with a flow rate of 1 mL/min. Calibration curve was linear over the concentration range of 25-2000 ng/mL. The retention times of nateglinide and internal standard (gliclazide) were 9.608 min and 11.821 min respectively. The developed RP-HPLC method can be successfully applied to the quantitative pharmacokinetic parameters determination of nateglinide in rabbit model.