The potential of ODFs as carriers for drugs/vaccines against COVID-19.

COVID-19 has spread out its wings across the globe and is taking away many lives. Millions of people are (self) quarantined to prevent the spread of this viral disease. World Health Organization (WHO) has affirmed that there is not any medicine for COVID-19. Besides, there is also no single drug that is approved by any regulatory agency for usage against this dangerous disease. Researchers across the globe are working tirelessly to fix an end to this virus and to save precious lives. While the research is in full swing, one is not sure whether they would come up with a chemical/herbal drug or a vaccine. Irrespective of the type of active ingredient for COVID-19, one needs to have a proper system to deliver the identified active ingredient to subjects/patients across the globe. Orodispersible films (ODFs) are excellent and attractive drug delivery carriers that have the potential to deliver drugs, herbal extracts, and vaccines. They are apt for patients who have a problem consuming traditional drug products such as tablets or capsules. The beauty of this dosage form is that it does not need water to consume by the subjects and can be readily administered to the tongue. The present review highlights the true potential of ODFs to act as a carrier for the delivery of various antiviral drugs/herbs/vaccines.

Printing Methods in the Production of Orodispersible Films.

Orodispersible film (ODF) formulations are promising and progressive drug delivery systems that are widely accepted by subjects across all the age groups. They are traditionally fabricated using the most popular yet conventional method called solvent casting method. The most modern and evolving method is based on printing technologies and such printed products are generally termed as printed orodispersible films (POFs). This modern technology is well suited to fabricate ODFs across different settings (laboratory or industrial) in general and in a pharmacy setting in particular. The present review provides an overview of various printing methods employed in fabricating POFs. Particularly, it provides insight about preparing POFs using inkjet, flexographic, and three-dimensional printing (3DP) or additive manufacturing techniques like filament deposition modeling, hot-melt ram extrusion 3DP, and semisolid extrusion 3DP methods. Additionally, the review is focused on patenting trends in POFs using ESPACENET, a European Patent Office search database. Finally, the review captures future market potential of 3DP in general and ODFs market potential in particular.

Nitrosamines crisis in pharmaceuticals - Insights on toxicological implications, root causes and risk assessment: A systematic review.

The presence of N-nitroso compounds, particularly N-nitrosamines, in pharmaceutical products has raised global safety concerns due to their significant genotoxic and mutagenic effects. This systematic review investigates their toxicity in active pharmaceutical ingredients (APIs), drug products, and pharmaceutical excipients, along with novel analytical strategies for detection, root cause analysis, reformulation strategies, and regulatory guidelines for nitrosamines. This review emphasizes the molecular toxicity of N-nitroso compounds, focusing on genotoxic, mutagenic, carcinogenic, and other physiological effects. Additionally, it addresses the ongoing nitrosamine crisis, the development of nitrosamine-free products, and the importance of sensitive detection methods and precise risk evaluation. This comprehensive overview will aid molecular biologists, analytical scientists, formulation scientists in research and development sector, and researchers involved in management of nitrosamine-induced toxicity and promoting safer pharmaceutical products.

Development and Characterization of Pullulan-Based Orodispersible Films of Iron.

Iron deficiency is the principal cause of nutritional anemia and it constitutes a major health problem, especially during pregnancy. Despite the availability of various non-invasive traditional oral dosage forms such as tablets, capsules, and liquid preparations of iron, they are hard to consume for special populations such as pregnant women, pediatric, and geriatric patients with dysphagia and vomiting tendency. The objective of the present study was to develop and characterize pullulan-based iron-loaded orodispersible films (i-ODFs). Microparticles of iron were formulated by a microencapsulation technique, to mask the bitter taste of iron, and ODFs were fabricated by a modified solvent casting method. Morphological characteristics of the microparticles were identified by optical microscopy and the percentage of iron loading was evaluated by inductively coupled plasma optical emission spectroscopy (ICP-OES). The fabricated i-ODFs were evaluated for their morphology by scanning electron microscopy. Other parameters including thickness, folding endurance, tensile strength, weight variation, disintegration time, percentage moisture loss, surface pH, and in vivo animal safety were evaluated. Lastly, stability studies were carried out at a temperature of 25 °C/60% RH. The results of the study confirmed that pullulan-based i-ODFs had good physicochemical properties, excellent disintegration time, and optimal stability at specified storage conditions. Most importantly, the i-ODFs were free from irritation when administered to the tongue as confirmed by the hamster cheek pouch model and surface pH determination. Collectively, the present study suggests that the film-forming agent, pullulan, could be successfully employed on a lab scale to formulate orodispersible films of iron. In addition, i-ODFs can be processed easily on a large scale for commercial use.

A Comprehensive Review of Patented Technologies to Fabricate Orodispersible Films: Proof of Patent Analysis (2000-2020).

Orodispersible films (ODFs)are ultra-thin, stamp-sized, rapidly disintegrating, and attractive oral drug delivery dosage forms best suited for the pediatric and geriatric patient populations. They can be fabricated by different techniques, but the most popular, simple, and industrially applicable technique is the solvent casting method (SCM). In addition, they can also be fabricated by extrusion, printing, electrospinning, and by a combination of these technologies (e.g., SCM + printing). The present review is aimed to provide a comprehensive overview of patented technologies of the last two decades to fabricate ODFs. Through this review, we present evidence to adamantly confirm that SCM is the most popular method while electrospinning is the most recent and upcoming method to fabricate ODFs. We also speculate around the more patent-protected technologies especially in the domain of printing (two or three-dimensional), extrusion (ram or hot-melt extrusion), and electrospinning, or a combination of the methods thereof.

Immune Repertoire and Advancements in Nanotherapeutics for the Impediment of Severe Steroid Resistant Asthma (SSR).

Severe steroid-resistant asthma (SSR) patients do not respond to the corticosteroid therapies due to the heterogeneity, and genome-wide variations. However, there are very limited reports pertinent to the molecular signaling underlying SSR and making pharmacologists, and formulation scientists to identify the effective therapeutic targets in order to produce novel therapies using novel drug delivery systems (NDDS). We have substantially searched literature for the peer-reviewed and published reports delineating the role of glucocorticoid-altered gene expression, and the mechanisms responsible for SSR asthma, and NDDS for treating SSR asthma using public databases PubMed, National Library of Medicine (NLM), google scholar, and medline. Subsequently, we described reports underlying the SSR pathophysiology through several immunological and inflammatory phenotypes. Furthermore, various therapeutic strategies and the role of signaling pathways such as mORC1-STAT3-FGFBP1, NLRP3 inflammasomes, miR-21/PI3K/HDAC2 axis, PI3K were delineated and these can be considered as the therapeutic targets for mitigating the pathophysiology of SSR asthma. Finally, the possibility of nanomedicine-based formulation and their applications in order to enhance the long term retention of several antioxidant and anti-asthmatic drug molecules as a significant therapeutic modality against SSR asthma was described vividly.

Orodispersible films: Conception to quality by design.

Orodispersible films (ODFs) are ultra-thin, stamp-sized, elegant, portable and patient-centric pharmaceutical dosage forms that do not need water to be ingested. They are particularly useful for paediatric and geriatric patient populations with special needs such as dysphagia, Parkinson's disease, and oral cancer. Accordingly, they hold tremendous potential in gaining patient compliance, convenience and pharmacotherapy. In the present review, conception and evolution of ODFs as a product and its technology are discussed. The review continues by providing overview about the potential of ODFs as carriers for delivering drugs, herbal extracts, probiotics and vaccines. Besides, strategies employed in drug cargo loading, taste masking of bitter drugs and enhancing drug stability are discussed. Finally, the review concludes by providing a brief overview about quality by design (QbD) principles in development of ODFs.

Characterization of Orodispersible Films: An Overview of Methods and Introduction to a New Disintegration Test Apparatus Using LDR - LED Sensors.

Orodispersible Film (ODF) is a promising and progressive dosage form that offers exceptional drug delivery benefits to patients. Indeed, they are the most transformational alternatives to traditional/conventional dosage forms such as tablets and capsules. ODFs are portable and highly comfortable for self-administration by patients with swallowing problems. The key to gain end-user acceptance is to have an ODF with outstanding quality. Poor quality may lead to choking or spitting, accordingly leading to a lack of compliance. It is vital to employ suitable experimental methodologies that facilitate characterization or determination of the quality of ODF. Nonetheless, there are no standard techniques prescribed in official compendia of any country. But, there is a consensus in the thin-film research community about the characterization techniques that one relies on deciding the quality of an ODF. We review various experimental techniques and highlight its importance in determining the performance and quality of an ODF. We provide a relatively novel and inventive disintegration test apparatus, which works using 'Light Dependent Resistor (LDR) and Light Emitting Diode (LED) sensors' for clear and accurate determination of start and end disintegration time of an ODF.

Patent Perspective on Orodispersible Films.

The traditional oral dosage forms (tablets, capsules, syrups, and elixirs) suffer from various disadvantages. They are pretty challenging to administer to patients with dysphagia, mucositis, and vomiting tendency. Therefore, gaining patient compliance using conventional dosage forms is highly cumbersome. One of the most transformative and innovative approaches to overcome such challenges is Orodispersible Films, a Novel Drug Delivery System. They are easy to consume, no need to chew or swallow and they do not even require water for consumption. Therefore, several drugs have been converted into orodispersible films to gain patient compliance. With the advent of these film formulations, new innovations are erupting and accordingly, companies in India are actively protecting them by filing ordinary patent applications in India and internationally under the Patent Cooperation Treaty. Patenting in India poses unique patentability challenges when compared with rest of the world. Nonetheless, meeting all the challenges and obtaining a valid patent not only help in recouping the cost involved in developing new drugs and its novel drug delivery systems but also helps in taking legal action against alleged infringers. This review article identifies key active Indian players in the domain of ODF based on their patent filings in India (and abroad) and also identifies the challenges they face to obtain a grant.