Efficacy and Safety of Ascending Dosages of Moxidectin and Moxidectin-albendazole Against Trichuris trichiura in Adolescents: A Randomized Controlled Trial.

BACKGROUND: Preventive chemotherapy is the main strategy to control soil-transmitted helminth (STH) infections. Albendazole and mebendazole are ubiquitously used, but they are not sufficiently effective against Trichuris trichiura. Moxidectin might be a useful addition to the small drug armamentarium. However, the optimal dosage of moxidectin alone and in combination with albendazole against T. trichiura and other STHs has not yet been determined. METHODS: A Phase II, randomized, placebo-controlled, dose-finding trial was conducted in 2 secondary schools on Pemba Island, Tanzania. Using a computer-generated list, T. trichiura-infected adolescents were randomly assigned to 7 treatment arms: 8, 16, or 24 mg of moxidectin monotherapy; 8, 16, or 24 mg of moxidectin plus 400 mg of albendazole combination therapy; or placebo. The primary outcome was cure rate (CR) against T. trichiura, analyzed 13 to 20 days after treatment by quadruple Kato-Katz thick smears. RESULTS: A total of 290 adolescents were enrolled (41 or 42 per arm). CRs against T. trichiura were 43, 46, and 44% for 8, 16, and 24 mg of moxidectin alone, respectively; 60, 62, and 66% for the same moxidectin dosages plus 400 mg of albendazole, respectively; and 12% for placebo. The moxidectin-albendazole arms also revealed higher CRs and egg reduction rates against hookworm than the monotherapy arms. Moxidectin and its combination with albendazole were well tolerated. CONCLUSIONS: Moxidectin-albendazole is superior to moxidectin. There is no benefit of using doses above 8 mg, which is the recommended dose for onchocerciasis. The moxidectin-albendazole combination of 8 mg plus 400 mg should be investigated further to develop recommendations for appropriate control of STH infections. CLINICAL TRIALS REGISTRATION: NCT03501251.

Shedding Light on Metal-Based Nanoparticles in Zebrafish by Computed Tomography with Micrometer Resolution.

Metal-based nanoparticles are clinically used for diagnostic and therapeutic applications. After parenteral administration, they will distribute throughout different organs. Quantification of their distribution within tissues in the 3D space, however, remains a challenge owing to the small particle diameter. In this study, synchrotron radiation-based hard X-ray tomography (SRµCT) in absorption and phase contrast modes is evaluated for the localization of superparamagnetic iron oxide nanoparticles (SPIONs) in soft tissues based on their electron density and X-ray attenuation. Biodistribution of SPIONs is studied using zebrafish embryos as a vertebrate screening model. This label-free approach gives rise to an isotropic, 3D, direct space visualization of the entire 2.5 mm-long animal with a spatial resolution of around 2 µm. High resolution image stacks are available on a dedicated internet page (http://zebrafish.pharma-te.ch). X-ray tomography is combined with physico-chemical characterization and cellular uptake studies to confirm the safety and effectiveness of protective SPION coatings. It is demonstrated that SRµCT provides unprecedented insights into the zebrafish embryo anatomy and tissue distribution of label-free metal oxide nanoparticles.

Pharmacokinetics and phenotyping properties of the Basel phenotyping cocktail combination capsule in healthy male adults.

AIMS: We compared the phenotyping metrics of a combination capsule formulation to its individual components of the newly composed Basel phenotyping cocktail. Moreover, we investigated a reduced sampling regimen for clinical applications. METHODS: We performed in vitro experiments and a crossover pharmacokinetic study in twelve healthy male subjects to compare the Basel phenotyping cocktail capsule containing 6 cytochrome P450 (CYP) probe drugs with individual administration of the same drugs. Parent compounds and selected metabolites were determined by liquid chromatography-tandem mass spectrometry. Metabolic ratios (MR) for are under the curve (AUC) and single time point measurements and their correlation were determined. RESULTS: Experiments with human liver microsomes and primary human hepatocytes in 3D co-culture confirmed that flurbiprofen is a suitable CYP2C9 substrate. Both cocktail formulations (capsule and individual probe drug administration) were well-tolerated and yielded reproducible MRs, which were almost identical. Correlations between single time point ratios and the corresponding AUC ratios depended on the sampling time point and the concentration time curve of the probe drugs. The MR of the capsule (Spearman rank correlation coefficient, Rs : 0.77-0.97) as well as the individual components (Rs : 0.69-0.99) correlated best at 6 h post-treatment considering all 6 CYPs. Moreover, the 2-h time points of the capsule agreed suitably with the AUC; however, the MR of omeprazole could not be determined for 10 out of 12 subjects. CONCLUSION: The capsule is easy to swallow, well tolerated and provides reliable estimates for CYP activity. The optimal sampling point for the capsule formulation is 6 h after intake.

[Abuse deterrent drug formulations for opioids]. / Missbrauch von Opioiden und mögliche Auswege aus der Opioid-Krise.

Abuse deterrent drug formulations for opioids Abstract. Misuse of opioids is an increasing problem. Significant medical and social consequences including overdose-related deaths have led to the declaration of an "opioid crisis". The present review article discusses the extent of the problem with a special focus on the situation in Switzerland. Measures are proposed including training of health care providers, regulatory intervention and technical solutions such as the design of abuse-deterrent formulations.

Stability investigation of FCC-based tablets for oral suspension with caffeine and oxantel pamoate as model drugs.

Tablets for oral suspension (TOS) present a convenient alternative dosage form to conventional tablets. Dispersed in a glass of water or on a spoon, such tablets can be easily administered, which can become beneficial for pediatric or geriatric patients. The novel excipient functionalized calcium carbonate (FCC), consisting of calcium carbonate and calcium phosphate, has already shown to be suitable to produce orally disintegrating placebo tablets. In this study, the influence of formulation composition on disintegration time in water and artificial saliva was investigated using caffeine and oxantel pamoate as model drugs, reflecting BCS class 1 and BCS class 4, respectively. The optimized formulation for each model drug underwent a stress test. The results show that the drug content in DTs was not influenced by FCC under stressed conditions, however the disintegration and dissolution performance was affected by temperature and humidity. It can be concluded that it was possible to produce TOS characterized by rapid disintegration complemented by high physical stability of the tablets and chemical stability of the drug.

Efficacy of Moxidectin Versus Ivermectin Against Strongyloides stercoralis Infections: A Randomized, Controlled Noninferiority Trial.

BACKGROUND: Infections with Strongyloides stercoralis are of considerable public health relevance. Moxidectin, a well-established drug in veterinary medicine under consideration for regulatory submission for the treatment of onchocerciasis, might serve as an alternative to the widely used ivermectin. METHODS: We conducted an exploratory, randomized, single-blind trial to evaluate the efficacy and safety of moxidectin (8 mg) vs ivermectin (200 µg/kg) against S. stercoralis infections. Cure rate (CR) against S. stercoralis was the primary outcome. Safety and efficacy against coinfections with soil-transmitted helminths and Opisthorchis viverrini were secondary outcomes. Noninferiority required the lower limit of the 95% confidence interval (CI) of the differences in CRs not exceed 7 percentage points. RESULTS: A total of 127 participants were enrolled and randomly assigned to the 2 treatments whereby 1 participant per arm was lost to follow-up. We observed a CR of 93.7% (59/63) for moxidectin compared to 95.2% (59/62) for ivermectin. Differences between CRs were estimated as -1.5% percentage points (95% CI, -9.6 to 6.5), thus the lower limit of the CI exceeds the noninferiority margin of 7 percentage points. No side effects were observed. CRs against hookworm infection were 57% (moxidectin) and 56% (ivermectin). Low efficacy for both drugs against O. viverrini was observed. CONCLUSIONS: Moxidectin might be a safe and efficacious alternative to ivermectin for the treatment of S. stercoralis infection, given that only slight differences in CRs were observed. However, noninferiority could not be demonstrated. Larger clinical trials should be conducted once the drug is marketed. CLINICAL TRIALS REGISTRATION: Current Controlled Trials: ISRCTN11983645.

Characterization of new functionalized calcium carbonate-polycaprolactone composite material for application in geometry-constrained drug release formulation development.

A new mineral-polymer composite (FCC-PCL) performance was assessed to produce complex geometries to aid in development of controlled release tablet formulations. The mechanical characteristics of a developed material such as compactibility, compressibility and elastoplastic deformation were measured. The results and comparative analysis versus other common excipients suggest efficient formation of a complex, stable and impermeable geometries for constrained drug release modifications under compression. The performance of the proposed composite material has been tested by compacting it into a geometrically altered tablet (Tablet-In-Cup, TIC) and the drug release was compared to commercially available product. The TIC device exhibited a uniform surface, showed high physical stability, and showed absence of friability. FCC-PCL composite had good binding properties and good compactibility. It was possible to reveal an enhanced plasticity characteristic of a new material which was not present in the individual components. The presented FCC-PCL composite mixture has the potential to become a successful tool to formulate controlled-release dosage solid forms.

Novel Polyurethane Matrix Systems Reveal a Particular Sustained Release Behavior Studied by Imaging and Computational Modeling.

The aim of the present work was to better understand the drug-release mechanism from sustained release matrices prepared with two new polyurethanes, using a novel in silico formulation tool based on 3-dimensional cellular automata. For this purpose, two polymers and theophylline as model drug were used to prepare binary matrix tablets. Each formulation was simulated in silico, and its release behavior was compared to the experimental drug release profiles. Furthermore, the polymer distributions in the tablets were imaged by scanning electron microscopy (SEM) and the changes produced by the tortuosity were quantified and verified using experimental data. The obtained results showed that the polymers exhibited a surprisingly high ability for controlling drug release at low excipient concentrations (only 10% w/w of excipient controlled the release of drug during almost 8 h). The mesoscopic in silico model helped to reveal how the novel biopolymers were controlling drug release. The mechanism was found to be a special geometrical arrangement of the excipient particles, creating an almost continuous barrier surrounding the drug in a very effective way, comparable to lipid or waxy excipients but with the advantages of a much higher compactability, stability, and absence of excipient polymorphism.

In silico and in vitro methods to optimize the performance of experimental gastroretentive floating mini-tablets.

CONTEXT: Development of floating drug delivery systems (FDDS) is challenging. To facilitate this task, an evaluation method was proposed, which allows for a combined investigation of drug release and flotation. OBJECTIVE: It was the aim of the study to use functionalized calcium carbonate (FCC)-based lipophilic mini-tablet formulations as a model system to design FDDS with a floating behavior characterized by no floating lag time, prolonged flotation and loss of floating capability after complete drug release. MATERIALS AND METHODS: Release of the model drug caffeine from the mini-tablets was assessed in vitro by a custom-built stomach model. A cellular automata-based model was used to simulate tablet dissolution. Based on the in silico data, floating forces were calculated and analyzed as a function of caffeine release. RESULTS AND DISCUSSION: Two floating behaviors were identified for mini-tablets: linear decrease of the floating force and maintaining of the floating capability until complete caffeine release. An optimal mini-tablet formulation with desired drug release time and floating behavior was developed and tested. CONCLUSION: A classification system for a range of varied floating behavior of FDDS was proposed. The FCC-based mini-tablets had an ideal floating behavior: duration of flotation is defined and floating capability decreases after completion of drug release.

Advanced analysis of disintegrating pharmaceutical compacts using deep learning-based segmentation of time-resolved micro-tomography images.

The mechanism governing pharmaceutical tablet disintegration is far from fully understood. Despite the importance of controlling a formulation's disintegration process to maximize the active pharmaceutical ingredient's bioavailability and ensure predictable and consistent release profiles, the current understanding of the process is based on indirect or superficial measurements. Formulation science could, therefore, additionally deepen the understanding of the fundamental physical principles governing disintegration based on direct observations of the process. We aim to help bridge the gap by generating a series of time-resolved X-ray micro-computed tomography (µCT) images capturing volumetric images of a broad range of mini-tablet formulations undergoing disintegration. Automated image segmentation was a prerequisite to overcoming the challenges of analyzing multiple time series of heterogeneous tomographic images at high magnification. We devised and trained a convolutional neural network (CNN) based on the U-Net architecture for autonomous, rapid, and consistent image segmentation. We created our own µCT data reconstruction pipeline and parameterized it to deliver image quality optimal for our CNN-based segmentation. Our approach enabled us to visualize the internal microstructures of the tablets during disintegration and to extract parameters of disintegration kinetics from the time-resolved data. We determine by factor analysis the influence of the different formulation components on the disintegration process in terms of both qualitative and quantitative experimental responses. We relate our findings to known formulation component properties and established experimental results. Our direct imaging approach, enabled by deep learning-based image processing, delivers new insights into the disintegration mechanism of pharmaceutical tablets.

Functionalized calcium carbonate as a novel pharmaceutical excipient for the preparation of orally dispersible tablets.

PURPOSE: To overcome the limitation of insufficient hardness during the production of rapidly disintegrating orally dispersible tablets (ODTs). Furthermore, we investigated the properties and usefulness of functionalized calcium carbonate (FCC) as a new pharmaceutical excipient for the production of ODTs. METHODS: A highly sensitive tensiometer-based method was developed to measure kinetics of weight loss during tablet disintegration. With this method we were able to determine the residence time of tablets placed on a basket immersed into a test medium. The shapes of tensiometer plots allowed us to categorize substances into four different types of disintegration. RESULTS: At the same volume and hardness, the tablet formulations with FCC showed a significantly higher porosity (over 60%) than all other formulations. Residence time depended mainly on the tablet composition rather than on porosity. When combined with disintegrants, FCC formulations exhibited favorable disintegration properties, comparable to those of the marketed drug risperidone oro (disintegration time ca. 10 s). CONCLUSIONS: Oral dosage forms--based on the new pharmaceutical excipient FCC--can be designed to have a short disintegration time combined with good mechanical strength. Due to these properties, FCC can be used for the preparation of ODTs.

The processes behind drug loading and release in porous drug delivery systems.

Porous materials are ubiquitous and exhibit properties suitable for depositing therapeutic compounds. Drug loading in porous materials can protect the drug, control its release rate, and improve its solubility. However, to achieve such outcomes from porous delivery systems, effective incorporation of the drug in the internal porosity of the carrier must be guaranteed. Mechanistic knowledge of the factors influencing drug loading and release from porous carriers allows rational design of formulations by selecting a suitable carrier for each application. Much of this knowledge exists in research areas other than drug delivery. Thus, a comprehensive overview of this topic from the drug delivery aspect is warranted. This review aims to identify the loading processes and carrier characteristics influencing the drug delivery outcome with porous materials. Additionally, the kinetics of drug release from porous materials are elucidated, and the common approaches to mathematical modeling of these processes are outlined.

Overcoming the clinical challenges of traditional ayahuasca: a first-in-human trial exploring novel routes of administration of N,N-Dimethyltryptamine and harmine.

Recently, the Amazonian plant medicine "ayahuasca"-containing the psychedelic compound N,N-dimethyltryptamine (DMT) and numerous ß-carboline alkaloids, such as harmine-has been suggested to exhibit beneficial effects in patients with affective and other mental health disorders. Although ayahuasca ingestion is considered safe, its pharmacokinetics/pharmacodynamics and tolerability profile pose some challenges and may limit the clinical applicability in vulnerable patient populations. While overdosing and the admixture of intolerable plant constituents may explain some of the common adverse reactions, the peroral route of administration may represent another relevant source of gastro-intestinal intolerabilities and unpredictable pharmacokinetics across users. To overcome these challenges, the present work aimed at creating ayahuasca-analogue formulations with improved pharmacokinetics and tolerability profiles. To this end, we developed peroral formulas and compared them with parenteral formulas specifically designed to circumvent the gastro-intestinal tract. In more detail, peroral administration of a capsule (containing purified DMT and harmine) was tested against a combined administration of an oromucosal harmine tablet and an intranasal DMT spray at two dose levels in an open-label within-subject study in 10 healthy male subjects. Pharmacokinetic and pharmacodynamic profiles were assessed by means of continuous blood sampling, vital sign monitoring, and psychometric assessments. Common side effects induced by traditional herbal ayahuasca such as nausea, vomiting, and diarrhea were significantly attenuated by our DMT/harmine formulations. While all preparations were well tolerated, the combined buccal/intranasal administration of harmine and DMT yielded substantially improved pharmacokinetic profiles, indicated by significantly reduced variations in systemic exposure. In conclusion, the combined buccal/intranasal administration of harmine and DMT is an innovative approach that may pave the way towards a safe, rapid-acting, and patient-oriented administration of DMT/harmine for the treatment of affective disorders. Clinical Trial Registration: clinicaltrials.gov, identifier NCT04716335.

High Acceptability of an Orally Dispersible Tablet Formulation by Children.

There is a high unmet medical need for child-appropriate oral dosage forms. The acceptability of a novel placebo orally dispersible tablet formulation (pODT) was therefore evaluated. Monolithic tablets contain an inorganic calcium carbonate/calcium phosphate carrier material as the main excipient. They were assessed in a cross-sectional acceptability study. The 40 child participants were between 2 to 5 years and 6 to 10 years old. One pODT with 5 mm diameter was administered to each participating child by placement on the tongue or into the buccal cavity. Parents were asked to complete a questionnaire together with the study personnel. The spontaneous reactions of the children were recorded. The ease of administration and children's acceptance of the tablet was rated by research staff on a 4-point acceptability scale and by parents on a 5-point Likert scale. The older subjects answered how they had liked the pODT by pointing to the appropriate face of a Facial Hedonic Scale. pODT had very high acceptability as 93% of parents, and all questioned children reported the formulation to be acceptable or very acceptable. Staff reported administering pODT in these children without problems. None of the children showed distress on receipt of pODT. We conclude that the proposed child-friendly dosage form provides a convenient option for oral drug administration and is expected to enhance drug-adherence in pediatric patients.

Metamizole is a Moderate Cytochrome P450 Inducer Via the Constitutive Androstane Receptor and a Weak Inhibitor of CYP1A2.

Metamizole is an analgesic and antipyretic drug used intensively in certain countries. Previous studies have shown that metamizole induces cytochrome (CYP) 2B6 and possibly CYP3A4. So far, it is unknown whether metamizole induces additional CYPs and by which mechanism. Therefore, we assessed the activity of 6 different CYPs in 12 healthy male subjects before and after treatment with 3 g of metamizole per day for 1 week using a phenotyping cocktail approach. In addition, we investigated whether metamizole induces CYPs by an interaction with the constitutive androstane receptor (CAR) or the pregnane X receptor (PXR) in HepaRG cells. In the clinical study, we confirmed a moderate induction of CYP2B6 (decrease in the efavirenz area under the plasma concentration time curve (AUC) by 79%) and 3A4 (decrease in the midazolam AUC by 68%) by metamizole. In addition, metamizole weakly induced CYP2C9 (decrease in the flurbiprofen AUC by 22%) and moderately CYP2C19 (decrease in the omeprazole AUC by 66%) but did not alter CYP2D6 activity. In addition, metamizole weakly inhibited CYP1A2 activity (1.79-fold increase in the caffeine AUC). We confirmed these results in HepaRG cells, where 4-MAA, the principal metabolite of metamizole, induced the mRNA expression of CYP2B6, 2C9, 2C19, and 3A4. In HepaRG cells with a stable knockout of PXR or CAR, we could demonstrate that CYP induction by 4-MAA depends on CAR and not on PXR. In conclusion, metamizole is a broad CYP inducer by an interaction with CAR and an inhibitor of CYP1A2. Regarding the widespread use of metamizole, these findings are of substantial clinical relevance.

Particle Forming Amorphous Solid Dispersions: A Mechanistic Randomized Pharmacokinetic Study in Humans.

Amorphous solid dispersions (ASDs) are a promising drug-delivery strategy to overcome poor solubility through formulation. Currently, the understanding of drug absorption mechanisms from ASDs in humans is incomplete. Aiming to gain insights in this matter, we conducted a randomized cross-over design open-label clinical study (NCT03886766) with 16 healthy male volunteers in an ambulatory setting, using micro-dosed efavirenz as a model drug. In three phases, subjects were administered (1) solid ASD of efavirenz 50 mg or (2) dissolved ASD of efavirenz 50 mg or (3) a molecular solution of efavirenz 3 mg (non-ASD) as a control in block-randomized order. Endpoints were the pharmacokinetic profiles (efavirenz plasma concentration vs. time curves) and derived pharmacokinetic parameters thereof (AUC0-t, Cmax, tmax, and ka). Results showed that the dissolved ASD (intervention 2) exhibited properties of a supersaturated solution (compared to aqueous solubility) with rapid and complete absorption of the drug from the drug-rich particles. All interventions showed similar AUC0-t and were well tolerated by subjects. The findings highlight the potential of particle forming ASDs as an advanced drug-delivery system for poorly soluble drugs and provide essential insights into underlying mechanisms of ASD functioning in humans, partially validating current conceptual models.

Colonic delivery of metronidazole-loaded capsules for local treatment of bacterial infections: A clinical pharmacoscintigraphy study.

Drug delivery to the colon offers great promise for local treatment of colonic diseases as it allows bypassing systemic absorption in the small intestine, thereby increasing luminal drug concentrations in the colon. The primary objective of this in vivo pharmaco-scintigraphy study was to assess the colon drug targeting accuracy of a metronidazole benzoate colonic drug delivery system intended for local treatment of Clostridioides difficile infections. Additionally, it was assessed if the concept of mucoadhesion would increase colonic residence time and promote higher drug bioavailability. Two different capsule formulations were designed and tested in healthy human subjects. Capsules contained either non-mucoadhesive (NM) or mucoadhesive (M) microgranules, both loaded with 100 mg metronidazole benzoate (antibiotic prodrug) and 5 mg samarium oxide (scintigraphy tracer). Filled capsules were coated with a colonic-targeting technology consisting of two functional layers, which allow for accelerated drug release mediated by the intestinal pH in combination with colonic bacteria. Coated capsules were neutron-activated to yield the radioisotope 153Sm prior to administration to 18 healthy subjects. Gamma-scintigraphy imaging was combined with the measurement of drug plasma levels. Formulation NM showed high colon-targeting accuracy. Initial capsule disintegration within the targeted ileocolonic region was observed in 8 out of 9 subjects (89%) with colonic arrival times in the range of 3.5-12 h and reduced systemic exposure. In contrast, the mucoadhesive formulation M showed some inconsistency regarding the site of initial capsule disintegration (targeting accuracy 56%). Variability of drug release was attributed to self-adhesion and agglomeration of the mucoadhesive microparticles within the capsule. Accurate ileocolonic delivery of metronidazole-loaded microgranules was achieved following oral administration of colonic-targeted capsules. Delayed drug release from NM microparticles in the colon leads to a reduced systemic exposure compared to immediate-release data from literature and presumably elevated drug concentrations in the colonic lumen. This approach offers promising options for the local treatment of colonic diseases.

Mechanisms of increased bioavailability through amorphous solid dispersions: a review.

Amorphous solid dispersions (ASDs) can increase the oral bioavailability of poorly soluble drugs. However, their use in drug development is comparably rare due to a lack of basic understanding of mechanisms governing drug liberation and absorption in vivo. Furthermore, the lack of a unified nomenclature hampers the interpretation and classification of research data. In this review, we therefore summarize and conceptualize mechanisms covering the dissolution of ASDs, formation of supersaturated ASD solutions, factors responsible for solution stabilization, drug uptake from ASD solutions, and drug distribution within these complex systems as well as effects of excipients. Furthermore, we discuss the importance of these findings on the development of ASDs. This improved overall understanding of these mechanisms will facilitate a rational ASD formulation development and will serve as a basis for further mechanistic research on drug delivery by ASDs.

Impact of Insoluble Separation Layer Mechanical Properties on Disintegration and Dissolution Kinetics of Multilayer Tablets.

Dissolution and disintegration of solid dosage forms such as multiple-layer tablet with different active ingredients depend on formulation and properties used in the formulations, and it may sometimes result in counterintuitive release kinetics. In this manuscript, we investigate the behavior of combined acetylsalicylic acid and mefenamic acid bi- and triple-layer formulations. We show that the simulation model with a cellular automata predicted the impact of the inert layer between the different active ingredients on each drug release and provide a good agreement with the experimental results. Also, it is shown that the analysis based on the Noyes-Whitney equation in combination with a cellular automata-supported dissolution and disintegration numerical solutions explain the nature of the unexpected effects. We conclude that the proposed simulation approach is valuable to predict the influence of material attributes and process parameters on drug release from multicomponent and multiple-layer pharmaceutical tablets and to help us develop the drug product formulation.

Spontaneous In Situ Formation of Liposomes from Inert Porous Microparticles for Oral Drug Delivery.

Despite the wide-spread use of liposomal drug delivery systems, application of these systems for oral purposes is limited due to their large-scale formulation and storage issues. Proliposomes are one of the formulation approaches for achieving solid powders that readily form liposomes upon hydration. In this work, we investigated a dry powder formulation of a model low-soluble drug with phospholipids loaded in porous functionalized calcium carbonate microparticles. We characterized the liposome formation under conditions that mimic the different gastrointestinal stages and studied the factors that influence the dissolution rate of the model drug. The liposomes that formed upon direct contact with the simulated gastric environment had a capacity to directly encapsulate 25% of the drug in situ. The emerged liposomes allowed complete dissolution of the drug within 15 min. We identified a negative correlation between the phospholipid content and the rate of water uptake. This correlation corroborated the results obtained for the rate of dissolution and liposome encapsulation efficiency. This approach allows for the development of solid proliposomal dosage formulations, which can be scaled up with regular processes.