Reader TTS

EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS Volume 176, July 2022, Pages 1-20 https://doi.org/10.1016/j.ejpb.2022.05.002Get rights and content ABSTRACT Powders for nasal delivery

have been recognized as advantageous dosage forms over liquids due to increased stability and residence time on nasal mucosa, with improved bioavailability. They can be manufactured by

spray-drying, allowing the optimization of the particle properties that are critical to guarantee nasal deposition, as size and shape. It is also a scalable and flexible method already

explored extensively in the pharmaceutical industry. However, it is important to understand how process parameters, particle physical properties and formulation considerations affect the

product performance. Hence, this review aims to provide an overview of nasal powder formulation and processing through spray drying, with an emphasis on the variables that impact on

performance. To this purpose, we describe the physical, biological and pharmacological phenomena prior to drug absorption as well as the most relevant powder properties. Formulation

considerations including qualitative and quantitative composition are then reviewed, as well as manufacturing considerations including spray drying relevant parameters. GRAPHICAL ABSTRACT

INTRODUCTION Nasal drug delivery has been recognized as an attractive route of administration for active pharmaceutical ingredients (API), both small molecules and biomacromolecules [98]. In

fact, this route can be a valuable alternative to oral delivery, since the nasal cavity has a large absorption surface area with high vascularization and permeability, leading to a quicker

drug absorption and hence a faster onset of action. Furthermore, it is non-invasive, painless and easily auto-administered, favoring patient compliance, relatively to parenteral

administration [106], [150]. Nasal route is the primary option for the treatment of topical nasal disorders. However, there has been a growing interest in using it for systemic treatments.

This is due to fast and direct absorption that circumvent the pre-systemic gastrointestinal and hepatic first-pass metabolism, allowing a quick onset of action and possible reduction of dose

[69]. Therefore, systemic delivery is mainly relevant for drugs that need rapid action such as pain management drugs [96]. Additionally, the olfactory epithelium allows unique contact

between external environment and central nervous system (CNS), enabling the intranasal drug to directly target the brain, circumventing the blood–brain barrier, commonly referred to as

nose-to-brain delivery. The targeted delivery through this pathway avoids side effects related to systemic delivery and improves efficacy of neurotherapeutics [116]. Nasal route has also

been studied for the administration of vaccines [127]. Despite the advantages, nasal administration has also some drawbacks that must be addressed during drug product development. First, the

low volume of nasal cavity limits the quantity of drug product that can be safely administrated. This is particularly challenging for drugs with poor solubility and/or permeability that may

require higher doses. Additionally, physiological and pathological conditions related to nasal mucosa may compromise the extent of nasal drug absorption and therapy efficacy [150], [185].

The mucociliary clearance removes the drug from the nasal epithelium by ciliary beating, reducing the time available for its direct transport of the drug through the nasal mucosa. However,

there are strategies to overcome some of these challenges, including formulation modification with excipients, including absorption enhancers and mucoadhesive agents, or using microparticles

as nasal drug delivery system [69], [135], [149], [150], [190]. Liquid formulations present some drawbacks like challenging chemical and microbiological stability, rapid clearance from the

nasal cavity and the need for high volumes to ensure the drug dosage. Solid formulations, represented by powders for nasal delivery, have as advantages their better chemical/microbiological

stability, improved residence time on the nasal cavity and enhanced systemic absorption due to an extended contact between powder and mucosa and the higher concentration gradient generated

across the mucosa [1],[41], [56], [113], [185]. Powders can also represent a simpler composition in excipients allowing larger quantities of drug to be administered [185]. The final dosage

form comprises the combination of the nasal powder formulation and a device for nasal insufflation. The interplay of nasal powder formulation and device is determinant for particle

deposition. Devices are determinant on the deposition pattern, and can be designed to target an area like the olfactory region for nose-to-brain delivery [204]. The angle and speed of

formulation cloud are critical factors on the deposition pattern related to the device [32], [35]. Nasal powders can be manufactured resorting to diverse methodologies including

lyophilization[38], [60], [100], [134], [155], [156], spray drying [1],[73], [76], [94], [105], [118], [184], supercritical fluid-assisted spray drying [39], spray freeze drying [72], [103],

[202]and agglomeration of micronized powders[16], [42], [78], [163], [162], [164]. In the literature, spray drying is one of the most often used for nasal powder preparation. It involves

the atomization and drying of a feed solution containing the API dissolved or dispersed in a liquid vehicle, which may or may not contain excipients, and collection of the powder. This

technology allows a controllable continuous processing and optimization of particle characteristics like size and shape [209], which may impact the drug therapeutic outcome [185]. However,

there are still some questions to be answered: how do these particle physical properties affect the final product performance? Which formulation attributes should be evaluated in the product

early development? How can all these variables influence the drug product quality and clinical performance? A few reviews have addressed in detail the anatomy and physiology of the nasal

cavity [98], [150], formulation and characterization of nasal products [28], [31], [143], [146], [149], [165], [190], in particular Salade et al. [165]et al. reviewed nasal products

characterization. Other reviews have addressed specifically nasal powder formulation [63], [185], with focus on Fasiolo et al. [185]who reviewed drug formulation and delivery by nasal route.

Herein, spray drying process will be focused on together with the formulation parameters that impact the performance of powders for nasal delivery. Some reviews have also addressed

immunotherapy and vaccination through dry powders [14], [19], [50], [92], [112], [186], but given their different mechanisms and characterization, these areas will not be addressed in this

review. Despite the advantages of powder formulations, there are only two nasal powders approved for systemic action: Onzetra® Xsail®, a sumatriptan product for migraine approved in 2016 by

Food and Drug Administration (FDA) [62] and Baqsimi™, a glucagon powder for severe hypoglycemia approved by FDA in 2019 [54]. For topical delivery, there are three nasal powders in the

market. A budesonide nasal powder is approved in Europe, while beclomethasone dipropionate and dexamethasone cipecilate nasal powders are available in Japan. These can be used in various

therapeutic indications, including for example the treatment of allergic rhinitis [102], [185]. Some barriers to the development and approval of more nasal powder products include the

shortage of available devices, lack of standardized characterization and performance methodologies and poor understanding of the impact of powders on negative sensory effects. These

challenges are further discussed on section 6. Regarding Onzetra® Xsail®, the nasal administration overcomes the oral associated drawbacks, namely, the high first-pass metabolism and nausea

and/or vomiting associated with migraines and the downside of subcutaneous injection-site reactions. The nasal powder shows faster absorption and higher peak plasma concentrations than the

correspondent nasal spray, which is important on rapid migraine relief [181]. In fact, most of the dose of nasal spray is swallowed, contrary to the nasal powder product [5]. BaqsimiTM aims

to bridge the need of a needle-free treatment for severe hypoglycemia outside the hospital setting [148]. Subcutaneous and intramuscular routes presuppose the preparation of solution and

injection by caregivers, which requires training, and often lead to erroneous or delayed administration [153]. Glucagon nasal powder is a portable, ready to use product, with comparable

efficacy to injectable glucagon [55]. The formulation includes solubility and absorption enhancers (beta-cyclodextrin and dodecylphosphocholine) and the particle size was designed to prevent

lung delivery [137], [153], [154]. Several drugs for nasal powder administration are being tested in clinical trials, including products for systemic and eventually nose-to-brain delivery,

as well as vaccines (Table 1), showing the interest of this delivery system, not only for academical research but also for the pharmaceutical industry. One example is the dihydroergotamine

(DHE) nasal powder, which has completed a Phase 1 safety, tolerability, and comparative bioavailability clinical trial with promising results [6]. This migraine acute treatment product

showed favorable DHE tolerability profile and resulted in plasma concentrations comparable to intramuscular administration and higher than the nasal spray. The only not injectable DHE

product approved is a liquid nasal spray that presents high variability of the pharmacokinetic profile and prolonged time to full dose administration [6]. This product could bridge the gap

between ease of administration and reliable and rapid absorption. SECTION SNIPPETS NASAL ANATOMY AND PHYSIOLOGY Nasal cavity is involved in breathing, olfaction and external environment

protection, and its anatomical and histological characteristics support these functions [150]. Human nasal cavity has a total volume of about 20 mL and a surface area of approximately 150 

cm2 [139]. The small size of the nasal cavity limits the maximum quantity of drug product to be administered to about 100–150 μL in case of liquid formulations [150]or 10–25 mg in case of

powder formulations [56], [119], [119]. Higher RELEVANT PROPERTIES OF POWDER FORMULATION FOR NASAL DELIVERY Formulation properties such as powder physical characteristics (particle size and

morphology, flowability, solid state) and biopharmaceutical profile (mucoadhesion and swelling, drug release and permeation) are critical on the rate and extent of drug absorption [25],

[185]. In addition to the airstream rate, which is limited by the selected device, particle size and morphology deeply impact on the particle impaction and therefore the aerodynamic profile

[117]. Flowability, defined as the ability FORMULATION COMPOSITION A powder formulation for nasal delivery can contain only the API, as the commercially available Onzetra® Xsail®, a

sumatriptan nasal powder. If the pure drug has a favorable pharmacokinetic profile and the active dose is high enough for handling and administration, excipients may not be needed, which is

advantageous from a safety, manufacturing and regulatory perspective [185]. However, many excipients can be added to address problems such as poor aerodynamic performance, difficult

MANUFACTURING AND FILLING PROCESSES CONSIDERATIONS The most important factor to consider on nasal powder manufacturing is ensuring particle size suitability, to guarantee deposition on the

nasal cavity. Formulation strategies include: engineered microparticles of the appropriate size [API-only or API and excipient (s)], powder blends and chimeral agglomerates (Table 3) [16],

[168], [185], [188]. Engineered microparticles (Fig. 3a and 3b) without any additional manufacturing steps are the most common nasal powder formulations studied in the OPPORTUNITIES AND

CHALLENGES Spray dried powders for nasal delivery represent an opportunity for drugs that require fast onset of action, systemic or nose-to-brain delivery, or high mucoadhesion for a

prolonged absorption. Amorphous dispersions may represent an extra opportunity for poorly soluble drugs, even though amorphization has not been completely exploited for nasal delivery. From

a manufacturing point of view, spray drying allows a fast, well controlled and scalable production, which are appreciated in the industry. CONCLUSIONS The nasal route is of great interest

for the administration of drugs that require fast systemic absorption or direct brain delivery. It is also an alternative for other delivery routes when these are associated with

limitations, such as pre-systemic hepatic metabolism in oral route or impossibility of self-administration in intravenous route. Powder dosage forms present significant advantages relative

to liquid formulations, namely better stability, increased mucoadhesion and the possibility of DECLARATION OF COMPETING INTEREST The authors declare that they have no known competing

financial interests or personal relationships that could have appeared to influence the work reported in this paper. ACKNOWLEDGMENTS This research was funded by FCT (Fundação para a Ciência

e Tecnologia), Portugal and Hovione under the doctoral fellowship PD/BDE/150298/2019. REFERENCES (210) * M. Abdel Mouez_ et al._ BIOAVAILABILITY ENHANCEMENT OF VERAPAMIL HCL VIA INTRANASAL

CHITOSAN MICROSPHERES EUR. J. PHARM. SCI. (2014) * A. Alhalaweh_ et al._ PREPARATION OF ZOLMITRIPTAN–CHITOSAN MICROPARTICLES BY SPRAY DRYING FOR NASAL DELIVERY EUR. J. PHARM. SCI. (2009) *

T.F. Bahamondez-Canas_ et al._ INTRANASAL IMMUNIZATION WITH DRY POWDER VACCINES EUR. J. PHARM. BIOPHARM. (2018) * A. Baldelli_ et al._ ANALYSIS OF COHESION FORCES BETWEEN MONODISPERSE

MICROPARTICLES WITH ROUGH SURFACES COLLOIDS SURFACES A PHYSICOCHEM. ENG. ASP. (2016) * A.G. Balducci_ et al._ ANTIDIURETIC EFFECT OF DESMOPRESSIN CHIMERA AGGLOMERATES BY NASAL ADMINISTRATION

IN RATS INT. J. PHARM. (2013) * C.R. Behl_ et al._ EFFECTS OF PHYSICOCHEMICAL PROPERTIES AND OTHER FACTORS ON SYSTEMIC NASAL DRUG DELIVERY ADV. DRUG DELIV. REV. (1998) * L.A. Bors_ et al._

MODULATION OF NOSE-TO-BRAIN DELIVERY OF A P-GLYCOPROTEIN (MDR1) SUBSTRATE MODEL DRUG (QUINIDINE) IN RATS BRAIN RES. BULL. (2020) * F. Buttini_ et al._ PARTICLES AND POWDERS: TOOLS OF

INNOVATION FOR NON-INVASIVE DRUG ADMINISTRATION J. CONTROL. RELEASE (2012) * K. Cal_ et al._ SPRAY DRYING TECHNIQUE. I: HARDWARE AND PROCESS PARAMETERS J. PHARM. SCI. (2010) * H. Calmet_ et

al._ FLOW FEATURES AND MICRO-PARTICLE DEPOSITION IN A HUMAN RESPIRATORY SYSTEM DURING SNIFFING J. AEROSOL SCI. (2018) * L. Casettari_ et al._ CHITOSAN IN NASAL DELIVERY SYSTEMS FOR

THERAPEUTIC DRUGS J. CONTROL. RELEASE (2014) * T. Cerchiara_ et al._ CHITOSAN AND POLY(METHYL VINYL ETHER-CO-MALEIC ANHYDRIDE) MICROPARTICLES AS NASAL SUSTAINED DELIVERY SYSTEMS EUR. J.

PHARM. BIOPHARM. (2005) * R. Chamanza_ et al._ A REVIEW OF THE COMPARATIVE ANATOMY, HISTOLOGY, PHYSIOLOGY AND PATHOLOGY OF THE NASAL CAVITY OF RATS, MICE, DOGS AND NON-HUMAN PRIMATES.

RELEVANCE TO INHALATION TOXICOLOGY AND HUMAN HEALTH RISK ASSESSMENT J. COMP. PATHOL. (2015) * J.Z. Chen_ et al._ IN VITRO ASSESSMENT OF AN IDEALIZED NOSE FOR NASAL SPRAY TESTING: COMPARISON

WITH REGIONAL DEPOSITION IN REALISTIC NASAL REPLICAS INT. J. PHARM. (2020) * K.H.H. Chen_ et al._ THE EFFECT OF POLYMER COATINGS ON PHYSICOCHEMICAL PROPERTIES OF SPRAY-DRIED LIPOSOMES FOR

NASAL DELIVERY OF BSA EUR. J. PHARM. SCI. (2013) * H.-J. Cho_ et al._ CHARACTERIZATION AND IN VITRO EVALUATION OF FREEZE-DRIED MICROPARTICLES COMPOSED OF GRANISETRON–CYCLODEXTRIN COMPLEX AND

CARBOXYMETHYLCELLULOSE FOR INTRANASAL DELIVERY INT. J. PHARM. (2010) * W. Cho_ et al._ DESIGN OF SALMON CALCITONIN PARTICLES FOR NASAL DELIVERY USING SPRAY-DRYING AND NOVEL SUPERCRITICAL

FLUID-ASSISTED SPRAY-DRYING PROCESSES INT. J. PHARM. (2015) * G. Colombo_ et al._ BRAIN DISTRIBUTION OF RIBAVIRIN AFTER INTRANASAL ADMINISTRATION ANTIVIRAL RES. (2011) * D. Coucke_ et al._

EFFECT ON THE NASAL BIOAVAILABILITY OF CO-PROCESSING DRUG AND BIOADHESIVE CARRIER VIA SPRAY-DRYING INT. J. PHARM. (2009) * A. Dalpiaz_ et al._ NASAL CHITOSAN MICROPARTICLES TARGET A

ZIDOVUDINE PRODRUG TO BRAIN HIV SANCTUARIES ANTIVIRAL RES. (2015) * A. Dalpiaz_ et al._ BRAIN UPTAKE OF AN ANTI-ISCHEMIC AGENT BY NASAL ADMINISTRATION OF MICROPARTICLES J. PHARM. SCI. (2008)

* A.M. Dolberg_ et al._ EXPRESSION OF P-GLYCOPROTEIN IN EXCISED HUMAN NASAL MUCOSA AND OPTIMIZED MODELS OF RPMI 2650 CELLS INT. J. PHARM. (2016) * E. Elmowafy_ et al._ NASAL

POLYSACCHARIDES-GLUCOSE REGULATOR MICROPARTICLES: OPTIMIZATION, TOLERABILITY AND ANTIDIABETIC ACTIVITY IN RATS CARBOHYDR. POLYM. (2014) * A. Fallacara_ et al._ IN VITRO CHARACTERIZATION OF

PHYSICO-CHEMICAL PROPERTIES, CYTOTOXICITY, BIOACTIVITY OF UREA-CROSSLINKED HYALURONIC ACID AND SODIUM ASCORBYL PHOSPHATE NASAL POWDER FORMULATION INT. J. PHARM. (2019) * E. Faulhammer_ et

al._ LOW-DOSE CAPSULE FILLING OF INHALATION PRODUCTS: CRITICAL MATERIAL ATTRIBUTES AND PROCESS PARAMETERS INT. J. PHARM. (2014) * S. Focaroli_ et al._ A DESIGN OF EXPERIMENT (DOE) APPROACH

TO OPTIMISE SPRAY DRYING PROCESS CONDITIONS FOR THE PRODUCTION OF TREHALOSE/LEUCINE FORMULATIONS WITH APPLICATION IN PULMONARY DELIVERY INT. J. PHARM. (2019) * A. Fortuna_ et al._ INTRANASAL

DELIVERY OF SYSTEMIC-ACTING DRUGS: SMALL-MOLECULES AND BIOMACROMOLECULES EUR. J. PHARM. BIOPHARM. (2014) * C. Freitas_ et al._ SPRAY-DRYING OF SOLID LIPID NANOPARTICLES (SLN(TM)) EUR. J.

PHARM. BIOPHARM. (1998) * E. Gavini_ et al._ NASAL ADMINISTRATION OF CARBAMAZEPINE USING CHITOSAN MICROSPHERES: IN VITRO/IN VIVO STUDIES INT. J. PHARM. (2006) * E. Gavini_ et al._ INFLUENCE

OF CHITOSAN GLUTAMATE ON THE IN VIVO INTRANASAL ABSORPTION OF ROKITAMYCIN FROM MICROSPHERES J. PHARM. SCI. (2011) * E. Gavini_ et al._ SPRAY-DRIED MICROSPHERES BASED ON METHYLPYRROLIDINONE

CHITOSAN AS NEW CARRIER FOR NASAL ADMINISTRATION OF METOCLOPRAMIDE EUR. J. PHARM. BIOPHARM. (2008) * C. Hasçiçek_ et al._ MUCOADHESIVE MICROSPHERES CONTAINING GENTAMICIN SULFATE FOR NASAL

ADMINISTRATION: PREPARATION AND IN VITRO CHARACTERIZATION FARM. (2003) * R. Hazlett_ et al._ APPROACHES FOR IMPROVING THE FLOWABILITY OF HIGH-PROTEIN DAIRY POWDERS POST SPRAY DRYING – A

REVIEW POWDER TECHNOL. (2021) * Y. He_ et al._ AMORPHOUS SOLID DISPERSIONS: UTILIZATION AND CHALLENGES IN DRUG DISCOVERY AND DEVELOPMENT J. PHARM. SCI. (2015) * Y. Huh_ et al._ PREPARATION

AND EVALUATION OF SPRAY-DRIED HYALURONIC ACID MICROSPHERES FOR INTRANASAL DELIVERY OF FEXOFENADINE HYDROCHLORIDE EUR. J. PHARM. SCI. (2010) * N.R. Hussein_ et al._ ADVANCES IN NASAL DRUG

DELIVERY SYSTEMS, IN: ADVANCES IN MEDICAL AND SURGICAL ENGINEERING (2020) * L. Illum NASAL DRUG DELIVERY—POSSIBILITIES, PROBLEMS AND SOLUTIONS J. CONTROL. RELEASE (2003) * L. Illum_ et al._

BIOADHESIVE STARCH MICROSPHERES AND ABSORPTION ENHANCING AGENTS ACT SYNERGISTICALLY TO ENHANCE THE NASAL ABSORPTION OF POLYPEPTIDES INT. J. PHARM. (2001) * K. AboulFotouh_ et al._ AMORPHOUS

SOLID DISPERSION DRY POWDER FOR PULMONARY DRUG DELIVERY: ADVANTAGES AND CHALLENGES INT. J. PHARM. (2020) * H. Akel_ et al._ PROGRESS AND PERSPECTIVES OF BRAIN-TARGETING LIPID-BASED

NANOSYSTEMS VIA THE NASAL ROUTE IN ALZHEIMER’S DISEASE EUR. J. PHARM. BIOPHARM. (2020) * A. Al-Khattawi_ et al._ THE DESIGN AND SCALE-UP OF SPRAY DRIED PARTICLE DELIVERY SYSTEMS EXPERT OPIN.

DRUG DELIV. (2018) * Z.T. Al-Salama_ et al._ SUMATRIPTAN NASAL POWDER: A REVIEW IN ACUTE TREATMENT OF MIGRAINE DRUGS (2016) * D. Albrecht_ et al._ A PHASE 1, RANDOMIZED, OPEN-LABEL, SAFETY,

TOLERABILITY, AND COMPARATIVE BIOAVAILABILITY STUDY OF INTRANASAL DIHYDROERGOTAMINE POWDER (STS101), INTRAMUSCULAR DIHYDROERGOTAMINE MESYLATE, AND INTRANASAL DHE MESYLATE SPRAY IN HEALTHY

ADULT SUBJECTS HEADACHE J. HEAD FACE PAIN (2020) * N. Alhajj_ et al._ DESIGNING ENHANCED SPRAY DRIED PARTICLES FOR INHALATION: A REVIEW OF THE IMPACT OF EXCIPIENTS AND PROCESSING PARAMETERS

ON PARTICLE PROPERTIES POWDER TECHNOL. (2021) * A. Alhalaweh_ et al._ SURFACE THERMODYNAMICS OF MUCOADHESIVE DRY POWDER FORMULATION OF ZOLMITRIPTAN AAPS PHARMSCITECH (2011) * D.J. Am Ende_

et al._ STRATEGIES TO ACHIEVE PARTICLE SIZE OF ACTIVE PHARMACEUTICAL INGREDIENTS * F. Araújo_ et al._ CHEMICAL MODIFICATION OF DRUG MOLECULES AS STRATEGY TO REDUCE INTERACTIONS WITH MUCUS

ADV. DRUG DELIV. REV. (2018) * P. Arora_ et al._ PERMEABILITY ISSUES IN NASAL DRUG DELIVERY DRUG DISCOV. TODAY. (2002) * B.J. Aungst ABSORPTION ENHANCERS: APPLICATIONS AND ADVANCES AAPS J.

(2012) * V.S. Belgamwar_ et al._ DESIGN AND DEVELOPMENT OF NASAL MUCOADHESIVE MICROSPHERES CONTAINING TRAMADOL HCL FOR CNS TARGETING DRUG DELIV. (2011) View more references CITED BY (35) *

INTEGRATED CONTINUOUS MANUFACTURING OF INHALABLE REMDESIVIR NANOAGGLOMERATE DRY POWDERS: DESIGN, OPTIMIZATION AND THERAPEUTIC POTENTIAL FOR RESPIRATORY VIRAL INFECTIONS 2023, International

Journal of Pharmaceutics Show abstract While inhalable nanoparticle-based dry powders have demonstrated promising potential as next-generation respiratory medicines, erratic particle

redispersibility and poor manufacturing reproducibility remain major hurdles hindering their translation from bench to bedside. We developed a one-step continuous process for fabricating

inhalable remdesivir (RDV) nanoagglomerate dry powder formulations by integrating flash nanoprecipitation and spray drying. The nanosuspension formulation was optimized using a three-factor

Box-Behnken design with a _z_-average particle size of 233.3 ± 2.3 nm and < 20% size change within six hours. The optimized inhalable nanoagglomerate dry powder formulation produced by

spray drying showed adequate aqueous redispersibility (_S_f/_S_i = 1.20 ± 0.01) and _in vitro_ aerosol performance (mass median aerodynamic diameter of 3.80 ± 0.58 µm and fine particle

fraction of 39.85 ± 10.16%). In A549 cells, RDV nanoparticles redispersed from the inhalable nanoagglomerate powders displayed enhanced and accelerated RDV cell uptake and negligible

cytotoxicity at therapeutic RDV concentrations. No statistically significant differences were observed in the critical quality attributes of the inhalable nanoagglomerate powders produced

from the continuous manufacturing and standalone batch modes. This work demonstrates the feasibility of large-scale continuous manufacturing of inhalable nanoagglomerate dry powder

formulations, which pave the way for their clinical translation. * INTRANASAL TRANSMUCOSAL DRUG DELIVERY: AN ALTERNATIVE APPROACH TO THE PARENTERAL ROUTE FOR MEDICAL EMERGENCIES 2023,

Journal of Drug Delivery Science and Technology Citation Excerpt : For example, a powder-based dosage form is not suitable for the parenteral route of administration unless a suitable

vehicle for reconstitution is available. At the same time, powders are advantageous for administration through the nasal route as it improves the bioavailability by enhancing the residence

time on the nasal mucosa [9]. Many preclinical and clinical studies have recently revealed that IN drug delivery is preferable than parenteral drug delivery in terms of its ease of use and

patient compliance. Show abstract Medical emergencies such as insulin-induced hypoglycaemia, anaphylactic reactions, seizures and opioid induced respiratory depression, need to be treated as

quickly as possible in order to prevent untoward life-threatening circumstances. The currently available therapeutic interventions mainly involve administration of drugs through the

parenteral route. However, the sophisticated administration related requirements of parenteral dosage forms, acts as a major concern for successful treatment of a medical emergency in

non-clinical settings. The intranasal (IN) route, owing to its ease of administration, non-invasiveness, and quick onset of action, can be a potential alternative to the parenteral route in

fulfilling the unmet needs of patients. Numerous attributes limit the nasal delivery of a drug, such as the nasal anatomy and physiology, physicochemical characteristics of the drug, and

formulation related parameters. Despite the challenges involved in IN delivery, many breakthrough formulations introduced in to the market, have demonstrated equivalent biopharmaceutical

performance to the parenteral route. This review critically discusses various IN marketed products which are currently in practice for treating medical emergencies in non-medical settings.

In particular, the review discusses dosage form design and excipient roles in developing drug products to be used to attain rapid rise in plasma concentration for producing a fast onset of

action similar to that of the parenteral intramuscular mode of drug administration. * DISCOVERY OF NEW COCRYSTALS BEYOND SERENDIPITY: LESSONS LEARNED FROM SUCCESSES AND FAILURES 2024,

CrystEngComm * THE ROLE OF ENGINEERED MATERIALS IN MUCOSAL VACCINATION STRATEGIES 2024, Nature Reviews Materials * CHITOSAN-BASED THERMOGELLING SYSTEM FOR NOSE-TO-BRAIN DONEPEZIL DELIVERY:

OPTIMISING FORMULATION PROPERTIES AND NASAL DEPOSITION PROFILE 2023, Pharmaceutics * SPRAY FREEZE DRYING OF BIOLOGICS: A REVIEW AND APPLICATIONS FOR INHALATION DELIVERY 2023, Pharmaceutical

Research View all citing articles on Scopus View full text © 2022 Elsevier B.V. All rights reserved.