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The buccal area of the oral mucosa provides an adorable channel of systemic medication distribution within the mouth mucosa. Drugs are delivered via oral mucosal layer, that has a higher first-pass metabolism and degrades gastrointestinal. The medication is immediately transmitted via the systemic circulation via the buccal drug delivery mechanism, which allows for painless administration, quick enzymatic action, high bioavailability, and reduced liver metabolism. The disadvantages of the oral drug delivery route include substantial presystemic metabolism, which causes medicines to a break down in an acidic environment due to poor absorption. Buccal delivery is an attractive administrative route due to its ease of delivery through the buccal mucosal membrane lining of the oral cavity. This review paper provides a comprehensive overview of the oral mucosa, mucoadhesion, variables influencing the whole process, assessment methodologies, and how to eliminate obstacles when formulating buccal drug delivery formulations.

The emerging branch in pharmaceutical sciences known as pharmaceutical nanotechnology presents new tools, opportunities and scope, which are expected to have significant applications, in disease diagnostics and therapeutics. There is a growing interest in nanobubble (NB) technology because of its wide range of potential applications in theranostics and targeted drug delivery including anticancer drug delivery, antibiotic delivery, gene delivery etc. Nanobubbles could offer several features in anticancer drug delivery, improving cellular uptake of chemotherapy drugs into cancer cell lines. Nanobubbles opened a new field of ultrasound imaging and were used as a diagnostic method. Generally, the delivery of drugs to organs and tissues is affected by two main ultrasound effects including the cavitation and sonoporation effects. This review describes the history of nanobubble, nomenclature, stability of nanobubble, physicochemical properties, characterization of nanobubble, method of preparation and applications. This article aims at highlighting the most recent and promising research trends including oxygen nanobubble, silica nanobubble and pluronicnanobubble and enlist the various drug delivery approaches involving the application of nanobubbles.

PFC (Pre-Submission Facility Correspondence) is the initial submission for an ANDA (Abbreviated New Drug Application), comprising information for the application similar to the original ANDA, and only valid in the United States Agency For a pre-determined inspection of the finished drug product's facility information. The Applicant can be introducing their Drug Product into the Market before the ANDA's Goal date of 8 months, according to the Pre-Submission Facility Correspondence. The submission type Original ANDA, PAS (Prior approval supplement), and PAS Amendment is based on prior review goal submission. The FDA (Food and Drug Administration) approves PFC submission for a range of reasons, including drug product shortfalls, COVID-19 emergency dosage medication, Patent paragraph-IV (patent is invalid or will not be infringed), and market-availability of one RLD (Reference listed drug) and one generic. The complete submission process gone through the eCTD submission format from the ESG (Electronic Submission Gateway).

Oral fast disintegrating films (OFDFs) have been developed as a viable alternative to conventional oral solid dosage forms such as tablets, capsules, and syrups for patients who struggle consuming them. OFDFs are thin strips that disintegrate or dissolve rapidly when placed in the oral cavity, allowing quick onset of action. These films are prepared by incorporating active pharmaceutical ingredients with film-forming polymers and other ingredients. OFDFs are also developed by incorporating active constituents present in phytochemicals such as flavonoids and polyphenols. In recent years, researchers have developed OFDFs by incorporating active phytoconstituents and/or herbal extracts to produce significant therapeutic activity. Phytochemical-based OFDFs show pharmacological activities such as anti-inflammatory, antiviral, immunomodulatory, antimigraine, antiarrhythmic, antioxidant and antibacterial. These films can also be used in the management of dementia, cerebral insufficiency and Alzheimer’s disease. The present review focuses on the formulation and development of phytochemical-loaded OFDFs and recent research carried out on the same in tabular form. Keywords: Oral fast disintegrating film, phytochemicals, active phytoconstituents, herbal extracts, natural active compounds, oral mucosa, mouth dissolving film

Silymarin is polyphenolic flavonoid obtained from the seeds of silybum marianum plant. It has various pharmacological properties such as hepatoprotective, anti-inflammatory, antioxidant, anti-carcinogenic, hypolipidemic properties. Silymarin has recently reported to be neuroprotective agent against neurodegenerative disease such as Alzheimer, Parkinson’s and cerebral ischemia. It contains eight active components, among which silibinin is the most active component. However, silymarin is BCS class II drug which having poor bioavailability due to extensive phase II metabolism, poor aqueous solubility, low permeability across intestinal epithelial cells and rapid excretion in bile and urine. Therefore, it is necessary to understand all formulations and analytical aspects including all possible future prospects. In this review a potential approach to enhance solubility, bioavailability and to develop a robust formulation is studied. The number of studies describes novel drug delivery system (NDDS) based formulations have been significantly increased. The raise in novel drug delivery exploitation is essentially due to defeated barriers within technological process of lipid based nanoparticles formulations and increased knowledge of underlying mechanisms of transport of NDDS via different route of administration. This review focuses on pharmacological properties of silymarin, challenges, benefits and application of novel drug delivery system. To reduce the adverse effects and toxicities novel drug delivery will be an attractive approach of current therapies. Keywords: Silymarin, route of administration, novel drug delivery, bioavailability, solubility

Nasal delivery is an alternative to oral or parenteral administration due to certain limitations such as absorption of the drug, drug targeting to particular organs can cause a problem for administration through oral route. The nasal route has also been successfully used for bypassing the blood-brain barrier and afterword delivering drug molecules to the central nervous system. Also, lag time related to oral drug delivery is reduces by this route and offers noninvasiveness, self-medication, patient comfort, and patient compliance. Extend drug delivery can be attained by different new dosage forms like in situ gel. In situ formulations are drug delivery systems. The in-situ gelling system is a process in which the solution forms of a gel before administration in the body, but once administrated, it undergoes gelation in-situ, to form a gel. In situ gelling system becomes very popular nowadays because of their several advantages over conventional drug delivery systems like a sustained and prolonged release of a drug, reduced Frequency of administration, improved patient compliance and comfort. Approaches towards the various formulation of in-situ gel concerning temperature, pH, and physicochemical conditions. The in situ gel-forming polymeric formulations offer several advantages like sustained and prolonged action reduced Frequency of administration, in comparison to conventional drug delivery systems. From a manufacturing point of view, the production of such systems is less complex and thus lowers the investment and manufacturing cost. Various evaluation parameters are considered during the preparation of In-Situ gel. Keywords: Nasal Drug Delivery, In Situ gel, gelation, polymers, etc

The blood-brain barrier (BBB) poses a major hurdle in the effective delivery of neuroactive drug molecules to the brain microenvironment. BBB hampers the neurotherapy of many neuro-ailments due to restrictive access of neurotherapeutics to the brain regions in desired concentrations. Direct transport of neurotherapeutics from the nose to the brain regions along the well-recognized olfactory and trigeminal nerve pathways seems to be an effective strategy to overcome the BBB, thereby enabling the functional recovery of major neurodegenerative disorders (NDs). The existence of a direct entry point from the nose to the brain encourages scientists to explore the opportunities in optimizing therapies of neuroailments. The present chapter comprehensively covers the neuropathogenesis of various NDs, associated therapeutic targets, and diagnosis of NDs. The authors have also illustrated the potential of nanobiosensors for the rapid detection of NDs. This chapter also highlights the nanotherapeutic strategies investigated for effectively delivering the neurotherapeutics to target the neuronal regions via a direct nose-to-brain transport pathway for effective management of NDs.

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Present work demonstrated the influence of novel amphiphilic carrier Soluplus® on the solubility and oral bioavailability of Morin hydrate (MOR). Spray-dried solid dispersions (SSD) were developed using the design of experiment (DoE). Saturation solubility study of the optimized formulation SSD F(7) showed many fold increment in the solubility with acceptable aqueous stability. In vitro drug diffusion kinetics suggested Weibull model to be the best fit. In vitro cytotoxicity assay revealed a significant increase in the anticancer potential compared to innate MOR. Furthermore, SSD F(7) showed 2.27-fold enhancement in the relative bioavailability as compared to MOR. BCS: biopharmaceutical classification system; MOR: Morin hydrate; SD: solid dispersion; SSD: spray dried solid dispersion; PM: physical mixture; CCD: central composite design; PSD: particle size distribution; PDI: polydispersity index; SEM: scanning electron microscopy; XRD: X-ray diffraction; DSC: differential scanning calorimetry; TGA: thermal gravimetric analysis; DTA: differential thermal analysis; DTG: derivative thermogravimetry; Tg: glass transition temperature; API: active pharmaceutical ingredient; P-gp: permeability glycoprotein; SRB: sulforhodamine B; ADR: adriamycin; DoE: design of experiment

In the present research, we report the synthesis and in vitro antimicrobial activity of a new series of novel quinazolino-thiadiazoles as fused pharmacophore (3–20). In general, the results of the in vitro antibacterial activity are encouraging, as out of 18 compounds tested, Compounds 3 and 8 with a 4-chlorophenyl and 4-nitro phenyl at C-2 of thiadiazole and chloromethyl substituent at C-2 of quinazolinone displayed a broad spectrum antimicrobial activity against all the strains, while compounds 13 and 16 again with a 4-chlorophenyl and 4-nitrophenyl at C-2 of thiadiazole and ethyl substituent at C-2 of quinazolinone showed the same potency but with a narrower spectrum (Bacterial and Fungal strains) with MIC values of 62.5 µg/ml. The structures of the compounds were confirmed by IR, 1H NMR, 13C NMR and Mass analysis. It is worth to mention that the combination of two biologically active moieties quinazoline and thiadiazole profoundly influences the biological activity.

N,N,N-trimethyl chitosan (TMC), a quaternized hydrophilic derivative of chitosan (CHT), outperformed the well-known solubility issues raised by CHT. The excellent properties offered by TMC provide it a significant edge for nanoparticle (NP) formation over other nanocarrier materials. Recently, TMC NPs have been applied to various fields like pharmaceutical, biomedical, biomaterials, and biotechnological field. The aim of this review is, therefore, to bring the TMC into the limelight so as to appraise it as an attractive functional polymer for nanomedicine applications which is facing oversight, at present, by regulatory agencies and manufacturers. The versatility of surface-tailoring, the capability of further chemical modifications, and the feasibility of ligand-conjugations in TMC polymer will further assist the scientists for reaching new dimensions in the nano-assembly of novel structures based on TMC.

Present work demonstrates the impact of sulfobutyl ether-β-cyclodextrin (SBE-β-CD, Captisol ® ) complexation on the solubility, dissolution and pH stability of the poorly soluble polyphenol chrysin (CHR) by freeze-drying technique. Phase solubility indicated the 1:1 stoichiometry. FTIR, DSC, PXRD, and SEM analysis confirmed the formation of inclusion complex. Moreover, 1 H NMR studies illustrated that the possible inclusion mode was through A-ring of the CHR which was further confirmed by molecular modelling. In addition, CHR/SBE-β-CD complex exhibited ∼108 times higher solubility and faster dissolution compared to CHR. The pH stability profile exhibited the protective effect of SBE-β-CD on the CHR at simulated pH. Also, in vitro cytotoxicity assay revealed an appreciable improvement in the anticancer activity of complex compared to free CHR, on MCF-7 and HeLa cell lines validating its superiority as a carrier.

The graph of drug resistance in cancer is reportedly increasing in terms of therapeutic efficiency. As per the WHO reports, around 70% of death reported in low- and middle-income countries. The increase in death toll was imparted from improper diagnosis and inadequate therapy. The 25% increase in disease burden may be laden due to resistance mutations in cancer during treatment. Exposure of high concentrations of chemotherapeutic agents leads to toxicity in the normal cells. Long-term conventional chemotherapy develops acquired resistance. The conventional therapeutics was not able to target the cancer cell specifically and need to promulgate the use of nanocarrier or bioengineering for the polychemotherapy. Phytochemicals are natural constituents providing alternative therapeutic approach to minimize the resistance. The present review highlights the nano-therapeutic approaches pondering over the conventional chemotherapy. The phytochemicals are extracted, isolated, and purified from daily dietary fibers or natural plants. Natural extractives act via multiple pathways and provide optimum effectiveness against resistance cancer. The poor solubility and bioavailability are major constraints in combination therapy. The nanotechnological approach improves the functional properties transportation across cell barriers, and improves bioavailability. The present review highlights the phytochemical based nanoformulations in improving the therapeutic response and several alternative ways to target resistance cancer. The major implications of phytochemical and chemotherapeutic combination therapy could lead in the future.

Present investigation deals with design, development and evaluation of chitosan-based spray-dried nasal mucoadhesive microspheres loaded with diltiazem hydrochloride (DTZ HCl). The principal objectives were to improve therapeutic efficacy through increased residence of microspheres on the nasal mucosa, and avoidance of hepatic first-pass metabolism. Formulation samples were characterized for preliminary physico–chemical parameters, mucoadhesiveness, drug release and release kinetics, mucosal toxicity, stability, and in vivo studies. Central composite experimental design was utilized herein to evaluate the influence of process and formulation variables product performance. Numerical and graphical optimization techniques were used for selecting optimum sample of prepared microspheres, further confirmed by three dimensional response surface plots and multilinear regression model. Results of ANOVA validated the significance of suggested models. Our findings suggest that DTZ-loaded spray-dried chitosan microspheres formulation could be used as a promising approach for intranasal administration which, in sum, improves therapeutic efficacy of the formulation.

The polyelectrolyte complexes (PECs) are versatile formulations formed by electrostatic interactions between oppositely charged biopolymers. PECs have been investigated widely by the researchers to explore the virtues of this formulation viz. high biocompatibility, excellent biodegradability, low toxicity, cost-effective, environment-friendly, and energy-efficient production. The prime object of the present review is to present the prominent features of PECs including mechanism of PEC formation, structural models of PECs, interactions involved in PEC formation, steps involved in PEC fabrication, factors affecting the formation of PECs and applications of PECs. The patents pertaining to PECs have briefly been tabulated as well.

A series of novel quinazoline derivatives were synthesized, virtually screened through different filters and evaluated for their anticonvulsant activity against electrically and chemically induced seizures, compared with that of the standard drugs methaqualone and sodium valproate. Compound 48, 3-(2-aminophenyl)-7-chloro-2-phenylquinazolin-4(3H)-one, was found to be the most potent compound of the series accompanied by relatively low neurotoxicity and low toxicity in the median lethal dose test as compared with the reference drugs. The obtained results showed that compounds 12, 48, 49 and 50 could be useful templates for future design, optimization, and investigation to construct more active analogs.

The near future of drug delivery system would lie in the search for a versatile and innocuous biomaterial, based mostly on natural resources. The tamarind seed xyloglucan (XG) is a natural neutral hemicellulose (hydrophilic polysaccharide) consisting of a main chain of glucan backbone with xylose and galactose side chains. XG is gifted with distinct mucoadhesive and in situ gelling properties which rated XG as an attractive, and functional polymer for numerous drug delivery applications. On these grounds, the present chapter is designed to underline the plausible potential of XG or XG-based systems in drug delivery. The feasibility of surface tailoring, the flexibility of chemical modification, and the possibility as ligand conjugations grant XG an extraordinary attention in the scientific community. The authors are assured that the versatility of XG would meet the expectations of regulatory authorities and the XG-based products will serve the therapeutic needs of the community in the coming years, if sufficiently investigated and promising outcomes are obtained in human subjects.

The brain-blood ratio is an important model correlating the brain-targeting ability of neurotherapeutics with the CNS pharmacokinetics, which need to be presented before the scientific community for exploration of its scientific worth. The purpose of this article is to bring this key concept and its precise discussion to the attention of the researchers.Three major points are discussed herein: First, the significance of brain-blood ratio with respect to investigational neurotherapeutics, and carrier systems and correlation of its research findings with the brain targeting efficiency. Second, the various factors influencing the brain-blood ratio. Third, the various strategies for enhancing the brain-blood ratio. In addition, the benchmark criteria for CNS-likeness of drug molecules and the correlation of brain-blood ratio with brain targeting ability of neurotherapeutics have been tabulated.The brain-blood ratio (also referred to as the brain-plasma ratio) represents one of the tools available today for estimation of CNS pharmacokinetics. It is preferred over other complicated techniques (in situ brain perfusion and microdialysis) due to its ease of use and practicality. We are optimistic that the brain-blood ratio offers an excellent way of evaluating brain-targeting efficiency of neurotherapeutics effectively. In our opinion, it is a very fundamental aspect of brain bioavailability and needs to be presented in a precise way.

The near future of drug delivery system would lie in the search of a versatile and innocuous material, based mostly on the natural resources. The tamarind seed xyloglucan (XG) is a natural neutral hemicellulose and a hydrophilic polysaccharide consisting of a main chain of glucan backbone with xylose and galactose side chains. XG is endowed with idiosyncratic mucoadhesive and in situ gelling properties which rated XG as an attractive, functional polymer for numerous drug delivery applications. In milieu of this, the present review is designed to underline the plausible potential of XG or XG-based systems in drug delivery. The feasibility of surface-tailoring, the flexibility of chemical-modification, and the possibility as ligand-conjugations grant XG an extraordinary consideration in the scientific territory. The authors are hopeful that the versatility of XG would meet the expectations of regulatory authorities and the XG-based products will serve the therapeutic needs of the community in the future, if sufficiently investigated and promising outcomes are obtained in human subjects.

Topical therapy is at the forefront in treating nail ailments (especially onychomycosis and nail psoriasis) due to its local effects, which circumvents systemic adverse events, improves patient compliance and reduces treatment cost. However, the success of topical therapy has been hindered due to poor penetration of topical therapeutics across densely keratinized nail plate barrier. For effective topical therapy across nail plate, ungual drug permeation must be enhanced. Present review is designed to provide an insight into prime aspects of transungual drug delivery viz. nail structure and physiology, various onychopathies, techniques of nail permeation enhancement and in vitro models for trans-nail drug permeation studies. Updated list of drug molecules studied across the nail plate and key commercial products have been furnished with sufficient depth. Patents pertinent to, and current clinical status of transungual drug delivery have also been comprehensively reviewed. This is the first systematic critique encompassing the detailed aspects of transungual drug delivery. In our opinion, transungual drug delivery is a promising avenue for researchers to develop novel formulations, augmenting pharmaceutical industries to commercialize the products for nail disorders.

Although chitosan (CHT, a linear cationic polysaccharide) is biodegradable, biocompatible, non-toxic, and mucoadhesive in nature, the low solubility of CHT in aqueous and alkaline media limits its applicability in pharmaceutical and biomedical field. This necessitate the introduction of new chemically-modified derivatives of CHT those can surmount the solubility barrier. Herein, N,N,N-trimethyl chitosan (TMC), a quaternized hydrophilic derivative of CHT, was synthesized by two-step reductive methylation of CHT and characterized for 1H NMR and zeta potential measurements. Polyelectrolyte complexes (PECs) based on TMC and dextran sulfate (DS) were prepared via ionic interactions between charged functional groups of former polysaccharides at different pH conditions (pH 5, 8, 10, and 12) and characterized for physicochemical (particle size and zeta potential) and solid- state characterizations (HR-TEM, SEM, FTIR, TGA and XRD). At alkaline pH conditions, the participant polymer chains (TMC and DS) are sufficiently close to form more stable PECs. The release efficiency was assessed after loading a model drug into optimized PEC formulation. Data indicated that the PECs fabricated at alkaline pH presents a reliable formulation for pharmaceutical and biomedical applications.

Nose to brain delivery of neurotherapeutics have been tried by several researchers to explore the virtues of this route viz. circumvention of BBB, avoidance of hepatic metabolism, practicality, safety, ease of administration and non-invasiveness. Nanoparticle (NP) therapeutics is an emerging modality for the treatment of Parkinson's disease (PD) as it offers targeted delivery and enhances the therapeutic efficacy and/or bioavailability of neurotherapeutics. This review presents a concise incursion into the nanomedicines suitable for PD therapy delivered via naso-brain transport. Clinical signs of PD, its pathophysiology, specific genetic determinants, diagnosis and therapy involved have been hashed out. Properties of brain-targeting NPs, transport efficacy and various nanocarriers developed so far also been furnished. In our opinion, nanotechnology-enabled naso-brain drug delivery is an excellent means of delivering neurotherapeutics and is a promising avenue for researchers to develop new formulations for the effective management of PD.