Inhalation Drug Research Articles

Mathematical and Computer Modeling as a Novel Approach for the Accelerated Development of New Inhalation and Intranasal Drug Delivery Systems

This paper presents modern methods of mathematical modeling, which are widely used in the development of new inhalation and intranasal drugs, including those necessary for the treatment of socially significant diseases, which include: tuberculosis, bronchial asthma, and mental and behavioral disorders. Based on the conducted studies, it was revealed that the methods of mathematical modeling used in the development of drugs are fragmented, and there is no single approach that would combine the existing methods. The results presented in the work should contribute to the development of a unified multiscale model as a new approach in mathematical modeling that contributes to the accelerated development and introduction to the market of new drugs with high bioavailability and the required therapeutic efficacy.

Progress of three kinds of treatment for asthma

Asthma is chronic inflammatory airway disease and may be induced by both genetic factors and epigenetic factors. Asthma has no particularly typical symptoms，and these symptoms include cough, expectoration, suffocation, chest tightness and even breathing difficulties. Drugs for asthma treatment are divided into rescue treatment and maintenance treatment, rescue treatments are for people with mild symptoms of asthma which means the frequency of onset does not exceed two times a week while maintenance treatments with inhalable drugs that deal with inflammation are for all other patients that suffer severely and to increase control. As in recent years, the population with asthma has shown to be increasing worldwide over time, the importance and necessity of understanding the mechanism of asthma and its main treatment methods and principles are also increasing. This article mainly focused on three types of most commonly seen maintenance treatment for asthma, including glucocorticoid, theophylline and leukotriene receptor antagonist.

Alprazolam (Xanax®) Inhalant Misuse: Associated Nasal Necrosis in a Young Healthy Patient

Abstract Inhalant drug abuse can result in sinonasal and pulmonary complications, including necrosis of the nasal cavity and upper aerodigestive tract. This case report focuses on a 26-year-old male who presented with nasal obstruction and was later diagnosed with endonasal necrosis associated with alprazolam (Xanax®) inhalation. Despite the known misuse of benzodiazepines, particularly through the oral route, inhalation remains a common method of misuse among adolescents. The patient’s symptoms improved after discontinuing alprazolam use and continuing nasal rinsing. The underlying mechanism of injury and the specific role of alprazolam inhalation in causing necrosis are not well understood, emphasizing the need for further research. Inhalant substance abuse is a significant issue among youth and young adults, necessitating targeted interventions and counseling to mitigate the potential gateway effect to more harmful substances.

Quality by design – Spray drying of ciprofloxacin-quercetin fixed-dose combination intended for inhalation

Spray drying is a well-suited technique for producing fixed-dose drug combinations. There has been a growing interest in utilizing spray drying to engineer carrier-free inhalable drug particles. The aim of this study was to understand and optimise the spray drying process of a ciprofloxacin-quercetin fixed dose combination intended for pulmonary administration. A 24-1 fractional factorial design and multivariate data analysis was used to identify important process parameters and investigate correlations with particle characteristics. The independent variables were solute concentration along with the processing parameters: solution flow rate, atomizing air flow rate and inlet temperature. The dependent variables included particle size distribution, yield and residual moisture content (RMC). Correlations between dependent and independent variables were further investigated via principal component analysis. Overall, solution flow rate, atomizing air flow rate and inlet temperature were found to affect the particle size D(v,50) and D(v,90) while the solute concentration and the atomizing air flow rate mainly affected the span. The inlet temperature was the most important parameter affecting the RMC and the yield. The formulation with optimized independent variables had a D(v,50) and span values of 2.42 µm and 1.81 with excellent process yield >70% and low RMC i.e. 3.4%. The optimized formulation was further investigated for its in vitro aerosolization performance using next generation impactor (NGI); it exhibited high emitted dose (ED > 80%) and fine particle fractions (FPF > 70%) for both drugs.

The effect of lung emptying before the inhalation of aerosol drugs on drug deposition in the respiratory system

The amount of drug depositing in the airways depends, among others, on the inhalation manoeuvre and breathing parameters. The objective of this study was to quantify the effect of lung emptying before the inhalation of drugs on the lung doses. Thirty healthy adults were recruited. Their breathing profiles were recorded while inhaling through six different emptied DPI devices without breathe-out and after comfortable or forced exhalation. The corresponding emitted doses and aerosol size distributions were derived from the literature. The Stochastic Lung Model was used to estimate the deposited doses. In general, forceful exhalation caused increased flow rate and inhaled air volume. Increased flow rate led to the increase of the average lung dose for drugs with positive lung dose-flow rate correlation (e.g. Symbicort®: relative increase of 6.7%, Bufomix®: relative increase of 9.2%). For drugs with negative correlation of lung dose with flow rate (all the studied drugs except the above two) lung emptying caused increased (Foster® by 2.7%), almost unchanged (Seebri®, Relvar®, Bretaris®) and also decreased (Onbrez® by 6.6%) average lung dose. It is worth noting that there were significant inter-individual differences, and lung dose of each drug could be increased by a number of subjects. In conclusion, the change of lung dose depends on the degree of lung emptying, but it is also inhaler and drug specific. Forceful exhalation can help in increasing the lung dose only if the above specificities are taken into account.

Evaluation of Inhaler Technique In COPD And Asthma Patients

Background: Asthma and COPD remain poorly controlled diseases that significantly affect the quality of life of patients. Inhalers are the main therapeutic options. Poor inhaler technique is a major factor that leads to poor clinical consequences, affecting the effectiveness of treatment and further control of symptoms. Aim of the Study: the present study aims at evaluating the inhaler technique and its clinical consequence in COPD and asthma patients .Patients and Methods: This is a cross sectional study of 70 patients, 35 with COPD and 35 with Asthma, who are already on inhaler drugs in their treatment. The use of inhaler was evaluated by a checklist that contains seven steps of inhaler use; by asking the patients to use their inhalers as usual, the correct or incorrect steps were recorded. The result of each patient checklist was correlated with the patient demographic parameters and level of control of his disease (COPD or asthma) by using COPD assessment test (CAT) or asthma control test (ACT) respectively. The Results: A total of 70 patients were enrolled in this study; 35 had COPD and 35 were asthmatic. The COPD patients were significantly older than asthmatic, mean age was 65.5 ± 5.8 (range: 55 – 75) years and 36.4 ± 13.9 (range: 16 – 65) years, respectively. (P. value < 0.05). Males were dominant among COPD patients than asthmatic group; they contribute to 80% and 45.7%, respectively,(P. value < 0.05). The level of education was not significantly different between the groups (P > 0.05). Current smokers were significantly more frequent in COPD group than in asthmatic group, 40% vs. 14.3%, respectively. The duration of inhaler use was significantly longer in asthmatics than in the COPD group members; the mean duration of use was 5.2 ± 4.5 (range: 1 – 20) years in asthmatic compared to 2.4 ± 1.1 (range: 1 – 6) years in COPD group. Dry powder inhalers (DPI) were relatively more frequently used than metered dose inhalers (MDI) where DPI used by 51.4% and 54.3% in COPD and asthmatic group, respectively. The level of education of patients and longer duration of inhaler use correlate positively with good technique, while no significant correlation with other variables. Conclusion: A large proportion of the participants had a poor inhaler technique regardless of the type of disease and of inhaler (DPI or MDI). There was a positive correlation between proper use of inhaler and high educational level of patients and longer duration of use.

Charge-Reduced Particles via Self-Propelled Electrohydrodynamic Atomization for Drug Delivery Applications.

Electrohydrodynamic atomization (EHDA) provides unparalleled control over the size and production rate of particles from solution. However, conventional methods produce highly charged particles that are not appropriate for inhalation drug delivery. We present a self-propelled EHDA system to address this challenge, a promising one-step platform for generating and delivering charge-reduced particles. Our approach uses a sharp electrode to produce ion wind, which reduces the cumulative charge in the particles and transports them to a target in front of the nozzle. We effectively controlled the morphologies of polymer products created from poly(vinylidene fluoride) (PVDF) at various concentrations. Our technique has also been proven safe for bioapplications, as evidenced by the delivery of PVDF particles onto breast cancer cells. The combination of simultaneous particle production and charge reduction, along with its direct delivery capability, makes the self-propelled EHDA a versatile technique for drug delivery applications.

Predicting the tolerability of inhalation therapy as a stage of a personalized approach in the treatment of children with cystic fibrosis

Background. Considering the features of basic therapy for chronic inflammatory bronchopulmonary process in cystic fibrosis (CF), which includes almost daily inhalation of pharmacological drugs (mucolytics, hypertonic saline (HS), antibiotics), evaluation of their tolerability is relevant in practice. The purpose of the study is to create a prognostic scale convenient for use in practical medicine, which would predict development of bronchial hyperreactivity syndrome in children with CF, based on clinical and anamnestic data, the results of molecular genetic research and inhalation tests with increasing concentrations of HS to prescribe personalized treatment. Materials and methods. The results of clinical and anamnestic, microbiological, biochemical, molecular and genetic studies and inhalation tests with increasing concentrations of HS were analyzed in 40 children with CF. The creation of the predictive algorithm was based on the application of correlation analysis, receiver operating characteristic analysis, binary logistic regression, Wald and Kullback method. Results. Two prognostic models have been created that can be used at different stages of providing medical care. Model 1 was built for the ambulatory stage of providing medical care to patients with CF, considering clinical and anamnestic data, molecular genetic predictors, as well as clinical symptoms during inhalation tests with increasing concentrations of HS. This model also can be used in young children who cannot perform spirometry to assess their external breathing function. For the highly specialized medical care, model 2 was created, which considers indicators of spirometric data of inhalation tests with increasing concentrations of HS and the level of exhaled nitric oxide. Conclusions. The developed models make it possible to calculate with high probability the risk of developing bronchial hyperreactivity to perform a personalized selection of HS and choose preventive brocholytic therapy as needed.

In vitro/In vivo Evaluation of Elastic Nano-lipid Carriers of Aztreonam for Pneumonic Lungs.

The liposomal inhalation of drugs has been extensively researched for the invasion of biofilms and macrophages in the infected lungs. The present study aimed to explore the in vitro and in vivo effects of elastic nano-lipid vesicles of aztreonam for pulmonary delivery. Elastic nano lipid vesicles of the drug were successfully prepared with the commonly abundant lung phospholipids (LIPOID S PC-3, LIPOID PC 16:0/16:0), cholesterol, and span 20. Four such formulations were evaluated for their physicochemical properties, in vitro diffusion, and cytotoxicity. The best formulation was subjected to stability, in vivo drug deposition on the pneumonic lungs, and histopathological studies. The characterization of the lipid vesicles in terms of particle size, zeta potential, and surface morphology confirmed the formation of stable nanolipid vesicles of the drug. The presence of surfactant in the lipid vesicles exhibited high bilayer stability, entrapment, and diffusion of the drug. The in vitro diffusion study revealed the biphasic characteristic with an initial burst, followed by sustenance for 8 h. A remarkable drug uptake was observed in the epithelial cell line of CHO Cricetulus griseus in the presence of surfactant. The drug was retained on the pneumonic lungs for 8 h. The histopathological study of lung tissue revealed that surfactant-based lipid vesicles could attenuate lung fibrosis significantly. It can be concluded that elastic nano lipid vesicular system of aztreonam could be a paradigm for targeting and localization of the drug with a long residence time in the lungs.

Abstracts from The Aerosol Society Drug Delivery to the Lungs 33.

Abstracts from The Aerosol Society Drug Delivery to the Lungs 33.

Pandemic-Related Changes in the Prevalence of Early Adolescent Alcohol and Drug Use, 2020–2021: Data From a Multisite Cohort Study

PurposeEvaluate changes in early adolescent substance use from May 2020 to May 2021 during the coronavirus disease 2019 pandemic using data from a prospective nationwide cohort: the Adolescent Brain Cognitive Development Study. MethodsIn 2018–2019, 9,270 youth aged 11.5–13.0 completed a prepandemic assessment of past-month alcohol and drug use, then up to seven during-pandemic assessments between May 2020 and May 2021. We compared the prevalence of substance use among same-age youth across these eight timepoints. ResultsPandemic-related decreases in the past-month prevalence of alcohol use were detectable in May 2020, grew larger over time, and remained substantial in May 2021 (0.3% vs. 3.2% prepandemic, p <.001). Pandemic-related increases in inhalant use (p = .04) and prescription drug misuse (p < .001) were detectable in May 2020, shrunk over time, and were smaller but still detectable in May 2021(0.1%-0.2% vs. 0% pre-pandemic). Pandemic-related increases in nicotine use were detectable between May 2020 and March 2021 and no longer significantly different from prepandemic levels in May 2021 (0.5% vs. 0.2% prepandemic, p = .09). There was significant heterogeneity in pandemic-related change in substance use at some timepoints, with increased rates among youth identified as Black or Hispanic or in lower-income families versus stable or decreased rates among youth identified as White or in higher-income families. DiscussionAmong youth ages 11.5–13.0 years old, rates of alcohol use remained dramatically reduced in May 2021 relative to prepandemic and rates of prescription drug misuse and inhalant use remained modestly increased. Differences remained despite the partial restoration of prepandemic life, raising questions about whether youth who spent early adolescence under pandemic conditions may exhibit persistently different patterns of substance use.

Dry Powder Inhalation for Lung Delivery in Cystic Fibrosis.

Pulmonary drug delivery has long been used for local and systemic administration of different medications used in acute and chronic respiratory diseases. Certain lung diseases, such as cystic fibrosis, rely heavily on chronic treatments, including targeted lung delivery. Pulmonary drug delivery possesses various physiological advantages compared to other delivery methods and is also convenient for the patient to use. However, the formulation of dry powder for pulmonary delivery proves challenging due to aerodynamic restrictions and the lower tolerance of the lung. The aim of this review is to provide an overview of the respiratory tract structure in patients with cystic fibrosis, including during acute and chronic lung infections and exacerbations. Furthermore, this review discusses the advantages of targeted lung delivery, including the physicochemical properties of dry powder and factors affecting clinical efficacy. Current inhalable drug treatments and drugs currently under development will also be discussed.

Effects of vocal fold lesions on particle deposition in a mouth-throat model: A numerical study

ObjectiveDysphonia is very common worldwide and aerosol drug inhalation is an important treatment for patients with dysphonia. This study aimed to explore the effects of vocal fold (VF) lesions on the particle deposition pattern using computational modeling. MethodsA realistic mouth-throat (MT) model of a healthy adult was constructed based on computed tomography images. Small and large vocal fold lesions were incorporated in the original model. A steady inhalation flowrate of 15 and 30 liter per minute (LPM) was used as the velocity inlet and monodisperse particles with diameters of 5 to 10 µm were simulated. ResultsParticles of larger size are more likely to be deposited in MT models, most of them distributed in oral cavity, oropharynx and supraglottis. The ideal sizes at 30 LPM ranged over 7-10 µm for healthy VFs and 6-8 µm for VF lesions. The best sizes at 15 LPM ranged over 6-8 µm for healthy VFs and 8-9 µm for VF lesions. ConclusionBased on this study, VF lesions influence the deposition pattern in the glottis obviously. The ideal sizes differ at the flow rates of 15 and 30 LPM.

Central and peripheral lung deposition of fluticasone propionate dry powder inhaler formulations in humans characterized by population pharmacokinetics.

This study aimed to gain an in-depth understanding of the pulmonary fate of three experimental fluticasone propionate (FP) dry powder inhaler formulations which differed in mass median aerodynamic diameters (MMAD; A-4.5µm, B-3.8µm and C-3.7µm; total single dose: 500µg). Systemic disposition parameter estimates were obtained from published pharmacokinetic data after intravenous dosing to improve robustness. A biphasic pulmonary absorption model, with mucociliary clearance from the slower absorption compartment, and three systemic disposition compartments was most suitable. Rapid absorption, presumably from peripheral lung, had half-lives of 6.9 to 14.6min. The peripherally deposited dose (12.6µg) was significantly smaller for formulation A-4.5µm than for the other formulations (38.7 and 39.3µg for B-3.8µm and C-3.7µm). The slow absorption half-lives ranged from 6.86 to 9.13hand were presumably associated with more central lung regions, where mucociliary clearance removed approximately half of the centrally deposited dose. Simulation-estimation studies showed that a biphasic absorption model could be reliably identified and that parameter estimates were unbiased and reasonably precise. Bioequivalence assessment of population pharmacokinetics derived central and peripheral lung doses suggested that formulation A-4.5µm lacked bioequivalence compared to the other formulations both for central and peripheral doses. In contrast, the other fomulations were bioequivalent. Overall, population pharmacokinetics holds promise to provide important insights into the pulmonary fate of inhalation drugs, which are not available from non-compartmental analysis. This supports the assessment of the pulmonary bioequivalence of fluticasone propionate inhaled formulations through pharmacokinetic approaches, and may be helpful for discussions on evaluating alternatives to clinical endpoint studies.

Inhalable Nanoparticle-based Dry Powder Formulations for Respiratory Diseases: Challenges and Strategies for TranslationalResearch.

The emergence of novel respiratory infections (e.g., COVID-19) and expeditious development of nanoparticle-based COVID-19 vaccines have recently reignited considerable interest in designing inhalable nanoparticle-based drug delivery systems as next-generation respiratory therapeutics. Among various available devices in aerosol delivery, dry powder inhalers (DPIs) are preferable for delivery of nanoparticles due to their simplicity of use, high portability, and superior long-term stability. Despite research efforts devoted to developing inhaled nanoparticle-based DPI formulations, no such formulations have been approved to date, implying a research gap between bench and bedside. This review aims to address this gap by highlighting important yet often overlooked issues during pre-clinical development. We start with an overview and update on formulation and particle engineering strategies for fabricating inhalable nanoparticle-based dry powder formulations. An important but neglected aspect in in vitro characterization methodologies for linking the powder performance with their bio-fate is then discussed. Finally, the major challenges and strategies in their clinical translation are highlighted. We anticipate that focused research onto the existing knowledge gaps presented in this review would accelerate clinical applications of inhalable nanoparticle-based dry powders from a far-fetched fantasy to a reality.

N,N,N-Trimethyl chitosan as a permeation enhancer for inhalation drug delivery: Interaction with a model pulmonary surfactant

N,N,N-Trimethyl chitosan (TMC), a biocompatible and biodegradable derivative of chitosan, is currently used as a permeation enhancer to increase the translocation of drugs to the bloodstream in the lungs. This article discusses the effect of TMC on a mimetic pulmonary surfactant, Curosurf®, a low-viscosity lipid formulation administered to preterm infants with acute respiratory distress syndrome. Curosurf® exhibits a strong interaction with TMC, resulting in the formation of aggregates at electrostatic charge stoichiometry. At nanoscale, Curosurf® undergoes a profound reorganization of its lipid vesicles in terms of size and lamellarity. The initial micron-sized vesicles (average size 4.8 μm) give way to a froth-like network of unilamellar vesicles about 300 nm in size. Under such conditions, neutralization of the cationic charges by pulmonary surfactant may inhibit TMC permeation enhancer capacity, especially as electrostatic charge complexation is found at low TMC content. The permeation properties of pulmonary surfactant-neutralized TMC should then be evaluated for its applicability as a permeation enhancer for inhalation in the alveolar region.

Liposomal Forms of Fluoroquinolones and Antifibrotics Decorated with Mannosylated Chitosan for Inhalation Drug Delivery.

The severe course of COVID-19 leads to the long-terming pulmonary diseases, such as bacterial pneumonia and post-COVID-19 pulmonary fibrosis. Thus, the essential task of biomedicine is a design of new effective drug formulations, including those for inhalation administration. In this work, we propose an approach to the creation of lipid-polymer delivery systems for fluoroquinolones and pirfenidone based on liposomes of various compositions decorated with mucoadhesive mannosylated chitosan. A generalizing study on the physicochemical patterns of the interactions of drugs with bilayers of various compositions was carried out, and the main binding sites were identified. The role of the polymer shell in the stabilization of vesicles and the delayed release of the contents has been demonstrated. For the liquid-polymer formulation of moxifloxacin, a prolonged accumulation of the drug in lung tissues was found after a single endotracheal administration to mice, significantly exceeding the control intravenous and endotracheal administration of the drug.

Comparison of 4.5% Versus 8% Sevoflurane for Inhalational Induction in Adults

Background: Inhalational induction is a frequently used anesthetic technique in pediatric patients. However, it is less frequently used in adult patients undergoing surgery. General anesthesia can be induced either by intravenous injection or inhalation of anesthetic drugs. There are no established guidelines about the usage of 4.5% vs 8% sevoflurane for inhalation induction in adults undergoing elective day care surgery. Aim: To compare mean time to loss of eyelash reflex using 4.5% vs 8% sevoflurane for inhalational induction in adult patients undergoing elective day care surgery. Methodology: This randomized controlled trial was conducted in the department of anesthesia, Mayo Hospital Lahoreover a period of six months from June 2018 to December 2018. A total of 60 patients were enrolled in the study. We included adult patients aged 18-60 years of either gender and ASA status I &amp; II undergoing elective day care surgery. While, patients having history of adverse reaction to inhalational agents and those who were on chronic sedatives, antipsychotic treatment were excluded. Demographic data of age and gender were obtained along with their body weight, height and BMI. They were randomly divided into two study groups using lottery method. After routine pre-op check and attaching standard anesthesia monitoring, patients in group-A and group-B were given 4.5% sevoflurane &amp; 8% sevoflurane respectively at a fresh gas flow of 8 L/min of oxygen and they were instructed to take deep breaths while inhaling gas with help of face mask. Results: The mean age in 4.5% sevoflurane group was 42.27±11.83 years while in 8% sevoflurane group it was 45.43±12.76 years. In 4.5% sevoflurane group there were 12(40%) male and 18(60%) female cases while in 8% sevoflurane group there were 11(36.67%) male and 19(63.33%) female cases. The mean time to loss of eyelash reflex in 4.5% sevoflurane group was 88.57±6.71 seconds and in 8% sevoflurane group the mean time to loss eyelashes reflex was 67.87±5.90 seconds. The mean time to loss eyelashes reflex was statistically less in 8% sevoflurane group, with p-value 0.001. Conclusion: We concluded that mean time to loss eyelashes reflex was considerably lesser with8% sevoflurane when compared with 4.5% sevoflurane for inhalational induction in adult patients for elective day care surgery. Keywords: Inhalational induction, sevoflurane, eyelash reflex, day care surgery.

Effect of transient breathing cycle on the deposition of micro and nanoparticles on respiratory walls

Background and objectiveFrom various perspectives (e.g. inhalation exposure and drug delivery), it is important to provide insights into the behavior of inhaled particles in the human respiratory system. Although most of the experimental and numerical studies have relied on an assumption of steady inhalation, the transient breathing profile is a key factor in particle deposition in the respiratory tract. In this study, particle transportation and deposition were predicted in a realistic human airway model during a breathing cycle and the effects of steady-state and transient flows on the deposition fraction were observed using computational fluid dynamics. MethodsTwo transient breathing cycles with different respiratory durations were considered to evaluate the effects of respiration duration on particle transport and deposition characteristics. Two types of steady breathing conditions with corresponding steady-state respiratory volumes were reproduced. The Lagrangian discrete phase model approach was used to investigate particle transportation and deposition under transient breathing conditions. Additionally, the Eulerian approach was used to analyze the transport of nanoparticles in the gas phase. A total of >50,000 monodispersed particles with aerodynamic diameters ranging between 2 nm and 10 μm were selected for comprehensive deposition predictions for particle sizes ranging from the nano- to microscale. ResultsThe predicted results were compared with the experimental data. The particle deposition fraction in the nasal cavity and tracheal regions showed differences between the steady and transient simulations. In addition, particle analysis under steady inhalation conditions cannot accurately predict particle transportation and deposition in the lower airway. Furthermore, the breathing cycle had a significant effect on the deposition fraction of the particles and the behavior of the inhaled particles. ConclusionsTransient simulation mimicking the breathing cycle was observed to be an important factor in accurately predicting the transportation and deposition of particles in the respiratory tract.

In Vitro Dissolution and Permeability Testing of Inhalation Products: Challenges and Advances.

In vitro dissolution and permeability testing aid the simulation of the in vivo behavior of inhalation drug products. Although the regulatory bodies have specific guidelines for the dissolution of orally administered dosage forms (e.g., tablets and capsules), this is not the case for orally inhaled formulations, as there is no commonly accepted test for assessing their dissolution pattern. Up until a few years ago, there was no consensus that assessing the dissolution of orally inhaled drugs is a key factor in the assessment of orally inhaled products. With the advancement of research in the field of dissolution methods for orally inhaled products and a focus on systemic delivery of new, poorly water-soluble drugs at higher therapeutic doses, an evaluation of dissolution kinetics is proving crucial. Dissolution and permeability testing can determine the differences between the developed formulations and the innovator's formulations and serve as a useful tool in correlating in vitro and in vivo studies. The current review highlights recent advances in the dissolution and permeability testing of inhalation products and their limitations, including recent cell-based technology. Although a few new dissolution and permeability testing methods have been established that have varying degrees of complexity, none have emerged as the standard method of choice. The review discusses the challenges of establishing methods that can closely simulate the in vivo absorption of drugs. It provides practical insights into method development for various dissolution testing scenarios and challenges with dose collection and particle deposition from inhalation devices for dissolution tests. Furthermore, dissolution kinetic models and statistical tests to compare the dissolution profiles of test and reference products are discussed.