Innovative Approaches to Enhance and Measure Medication Adherence in Chronic Disease Management: A Review.

Medication non-adherence is a problem that affects up to 50% of patients with chronic diseases. The result is a failure to achieve therapeutic goals and an increased burden on the healthcare system. It is, therefore, highly appropriate to develop models to assess patient adherence to prescribed therapy. To date, there are many methods for doing this. However, several tools have been developed that subjectively or objectively, directly or indirectly, assess the level of patient adherence. Electronic medication packaging devices are among the most rapidly evolving methods of measuring adherence. Other emerging technologies include the use of artificial intelligence algorithms and ingestible biosensors. The former is being used to create applications for mobile phones and laptops. The latter appears to be the least susceptible to the risk of overestimating adherence but remains very expensive. Here, we present recent developments in measuring patient adherence, and provide details of achievements in objective methods for assessing adherence, such as electronic monitoring devices, video-observed therapy, and ingestible biosensors. A dedicated section on using artificial intelligence and machine learning in adherence measurement and reviewing questionnaires and scales used in specific diseases is also included. Methods are discussed along with their advantages and potential limitations. This article aimed to review current measures and future initiatives to improve patient medication adherence.

Coated Microneedle System for Delivery of Clotrimazole in Deep-Skin Mycoses.

Mycoses of the skin are infectious diseases caused by fungal microorganisms that are generally treated with topical agents. However, such therapy is often ineffective and has to be supported by oral use of active substances, which, in turn, can cause many side effects. A good alternative for the treatment of deep-skin mycoses seems to be microneedles (MNs). The aim of this research was to fabricate and evaluate the properties of innovative MNs coated with a hydrogel as potential carriers for clotrimazole (CLO) in the treatment of deep fungal skin infections. A 3D printing technique using a photo-curable resin was employed to produce MNs, which were coated with hydrogels using a dip-coating method. Hydrogels were prepared with carbopol EZ-3 Polymer (Lubrizol) in addition to glycerol and triisopropanolamine. Clotrimazole was introduced into the gel as the solution in ethanol or was suspended. In the first step of the investigation, a texture analysis of hydrogels was prepared with a texture analyzer, and the drug release studies were conducted with the use of automatic Franz diffusion cells. Next, the release profiles of CLO for coated MNs were checked. The last part of the investigation was the evaluation of the antifungal activity of the prepared systems, and the inhibition of the growth of Candida albicans was checked with the diffusion and suspended-plate methods. The texture profile analysis (TPA) for the tested hydrogels showed that the addition of ethanol significantly affects the following studied parameters: hardness, adhesiveness and gumminess, causing a decrease in their values. On the other hand, for the gels with suspended CLO, better spreadability was seen compared to gels with dissolved CLO. The presence of the active substance did not significantly affect the values of the tested parameters. In the dissolution study, the results showed that higher amounts of CLO were released for MNs coated with a hydrogel containing dissolved CLO. Also, microbiological tests proved its efficacy against fungal cultures. Qualitative tests carried out using the diffusion method showed that circular zones of inhibition of fungal growth on the plate were obtained, confirming the hypothesis of effectiveness. The suspension-plate technique confirmed the inhibitory effect of applied CLO on the growth of Candida albicans. From the analysis of the data, the MNs coated with CLO dissolved in hydrogel showed better antifungal activity. All received results seem to be helpful in developing further studies for MNs as carriers of antifungal substances.

Use of Collagen in Cosmetic Products.

Collagen (CLG) belongs to the family of fibrillar proteins and is composed of left-handed α polypeptide chains, which, twisting around themselves and their axis, form a right-handed superhelix. In the chemical structure, it contains mainly proline, hydroxyproline, glycine, and hydroxylysine. It occurs naturally in the dermis in the form of fibers that provide the skin with proper density and elasticity. The review aimed to present the types of collagen protein, factors affecting its structure and its unusual role in the functioning of the human body. Also, an overview of cosmetic products containing collagen or its derivatives, the characteristics of the formulas of these products, and the effects of their use were presented. Throughout the market, there are many cosmetic and cosmeceutical products containing CLG. They are in the form of fillers administered as injections, belonging to the group of the oldest tissue fillers; products administered orally and for topical use, such as creams, gels, serums, or cosmetic masks. Analyzed studies have shown that the use of products with collagen or its peptides improves the general condition of the skin and delays the aging process by reducing the depth of wrinkles, improving hydration (in the case of oral preparations), reducing transepithelial water loss (TEWL), as well as improving skin density and elasticity. In addition, oral application of bioactive CLG peptides has shown a positive effect on the nails, reducing the frequency of their breakage.

Perception of Polish pharmacy students on simulation exercise in pharmaceutical care for diabetes-a pilot study.

BACKGROUND: The transformation of a pharmacist's role from that of a drug dispenser to an advisor and patient educator, partially accelerated by the COVID-19 pandemic, requires a thorough change in the pharmacy curriculum. Preparation for the provision of modern pharmaceutical services requires the use of the most advanced teaching methods, such as pharmaceutical simulation. Knowledge alone does not guarantee students' readiness and motivation to take on new challenges in their professional work, but it seems crucial that graduates of medical faculties have the ability to practically apply their knowledge, including in new and nonstandard situations. Therefore, in our study, we proposed an intervention using a simulation method (peer role play) in teaching pharmaceutical care, and we assessed its impact on students' levels of self-perceived confidence and self-efficacy in accordance with Bandura's theory. The aim of the study was to verify whether the introduction of these types of classes could be a useful element of pharmacy curriculum renewal. METHODS: The questionnaire-based study was conducted during pharmaceutical care peer role-playing classes in a simulation environment with a debriefing session among 85 final-year pharmacy students at Poznan University of Medical Sciences, Poland. The questionnaire consisted of two surveys: the General Self-Efficacy Scale (GSE) and a pre-post self-assessment and self-efficacy questionnaire. RESULTS: There was a positive correlation between the GSE score and self-efficacy (R = 0.52, p < 0.0001). A statistically significant increase in the post-self-assessment of all the skills and competencies included in the survey in the field of pharmaceutical care of a patient with diabetes compared to the pre-values was also observed (p < 0.001). Additionally, the students' self-efficacy in terms of communicating with patients was greater following the class than before the class (p < 0.001). CONCLUSIONS: The peer role-play active teaching method was found to be a cost-effective method allowing for an increase in the self-assessment and self-efficacy of pharmacy students in diabetic patient pharmaceutical care. However, further in-depth research is needed to fully confirm the effectiveness of simulation exercises for teaching pharmacy undergraduates.

Photopolymer-Based Composite with Substance Release Capability Manufactured Additively with DLP Method.

In this study, caffeine-loaded photoresin composites with homogeneous structures, suitable for additive manufacturing of transdermal microneedle systems, were obtained. The properties of the composites with varying caffeine concentrations (0.1-0.4% w/w) were investigated for carbon-carbon double bond conversion using Fourier Transform Infrared Spectroscopy, surface wettability and mechanical properties using a static tensile test and nanoindentation, and caffeine release in ethanol using UV-Vis. The caffeine concentration did not affect the final degree of double bond conversion, which was confirmed in tensile tests, where the strength and Young's modulus of caffeine-loaded samples had comparable values to control ones. Samples with 0.1 and 0.2% caffeine content showed an increase in nanohardness and reduced elastic modulus of 50 MPa and 1.5 MPa, respectively. The good wettability of the samples with water and the increase in surface energy is a favorable aspect for the dedicated application of the obtained composite materials. The amount of caffeine released into the ethanol solution at 1, 3 and 7 days reached a maximum value of 81%, was higher for the lower concentration of caffeine in the sample and increased over time. The conducted research may enhance the potential application of composite materials obtained through the digital light processing method in additive manufacturing.

3D-printed solid oral dosage forms for mental and neurological disorders: recent advances and future perspectives.

INTRODUCTION: 3D printing (3DP) applications in medicine are intensively investigated, creating an opportunity to provide patient-tailored therapy by delivering a drug with an accurate dose and release profile. Moving away from the 'one size fits all' paradigm, it could be beneficial for treating mental and neurological disorders, improving the efficiency and safety of the therapy. The aim of this critical review is to assess recent advances and identify gaps regarding 3DP in this important and challenging field, by focusing on recent research examples. AREAS COVERED: Applications of the 3DP techniques for solid dosage forms in mental and neurological disorders have been covered and discussed, together with recent advantages, limitations, and future directions. EXPERT OPINION: The personalize treatment, which is considered as the most significant advantage of the 3DP technique, can be beneficial in mental and neurological disorders therapy, where the dose should be adjusted to the patient. Printing of medicines enables creating the structure modifications and thus controlling the drug release or combining multiple drugs into one tablet, simplifying the dose regimen. Medications printed on-demand, in health-care facilities, could address the special needs of pediatric patients and help avoid interruptions in the supply chain. Despite promising advances, the described methods have limitations and need further investigation before being scaled-up to an industrial manufacturing environment. There is also a need to establish protocols for the preparation and registration of 3DP dosage forms.

Phototoxic or Photoprotective?-Advances and Limitations of Titanium (IV) Oxide in Dermal Formulations-A Review.

The widespread role of titanium (IV) oxide (TiO2) in many industries makes this substance of broad scientific interest. TiO2 can act as both a photoprotector and photocatalyst, and the potential for its role in both applications increases when present in nanometer-sized crystals. Its sunlight-scattering properties are used extensively in sunscreens. Furthermore, attempts have been made to incorporate TiO2 into dermal formulations of photolabile drugs. However, the propensity to generate reactive oxygen species (ROS) rendering this material potentially cytotoxic limits its role. Therefore, modifications of TiO2 nanoparticles (e.g., its polymorphic form, size, shape, and surface modifications) are used in an effort to reduce its photocatalytic effects. This review provides an overview of the potential risks arising from and opportunities presented by the use of TiO2 in skin care formulations.

Alginate-Based Materials Loaded with Nanoparticles in Wound Healing.

Alginate is a naturally derived polysaccharide widely applied in drug delivery, as well as regenerative medicine, tissue engineering and wound care. Due to its excellent biocompatibility, low toxicity, and the ability to absorb a high amount of exudate, it is widely used in modern wound dressings. Numerous studies indicate that alginate applied in wound care can be enhanced with the incorporation of nanoparticles, revealing additional properties beneficial in the healing process. Among the most extensively explored materials, composite dressings with alginate loaded with antimicrobial inorganic nanoparticles can be mentioned. However, other types of nanoparticles with antibiotics, growth factors, and other active ingredients are also investigated. This review article focuses on the most recent findings regarding novel alginate-based materials loaded with nanoparticles and their applicability as wound dressings, with special attention paid to the materials of potential use in the treatment of chronic wounds.

Natural Gums in Drug-Loaded Micro- and Nanogels.

Gums are polysaccharide compounds obtained from natural sources, such as plants, algae and bacteria. Because of their excellent biocompatibility and biodegradability, as well as their ability to swell and their sensitivity to degradation by the colon microbiome, they are regarded as interesting potential drug carriers. In order to obtain properties differing from the original compounds, blends with other polymers and chemical modifications are usually applied. Gums and gum-derived compounds can be applied in the form of macroscopic hydrogels or can be formulated into particulate systems that can deliver the drugs via different administration routes. In this review, we present and summarize the most recent studies regarding micro- and nanoparticles obtained with the use of gums extensively investigated in pharmaceutical technology, their derivatives and blends with other polymers. This review focuses on the most important aspects of micro- and nanoparticulate systems formulation and their application as drug carriers, as well as the challenges related to these formulations.

Orodispersible Films-Current State of the Art, Limitations, Advances and Future Perspectives.

Orodispersible Films (ODFs) are drug delivery systems manufactured with a wide range of methods on a big scale or for customized medicines and small-scale pharmacy. Both ODFs and their fabrication methods have certain limitations. Many pharmaceutical companies and academic research centers across the world cooperate in order to cope with these issues and also to find new formulations for a wide array of APIs what could make their work profitable for them and beneficial for patients as well. The number of pending patent applications and granted patents with their innovative approaches makes the progress in the manufacturing of ODFs unquestionable. The number of commercially available ODFs is still growing. However, some of them were discontinued and are no longer available on the markets. This review aims to summarize currently marketed ODFs and those withdrawn from sale and also provides an insight into recently published studies concerning orodispersible films, emphasizing of utilized APIs. The work also highlights the attempts of scientific communities to overcome ODF's manufacturing methods limitations.

The role of active learning methods in teaching pharmaceutical care - Scoping review.

Background: The pharmacists in a community pharmacies have already provided, or will provide in the near future advanced pharmaceutical care services. This requires modifying the approach to teaching pharmacy students as well as adapting the curriculum to the changing professional realities. It has been proven that in the field of medical and related sciences, learners-centered active teaching methods allow to achieve learning outcomes effectively, especially in the field of practical skills. Objectives: As the pharmaceutical services are only being introduced in many European countries, the question arises as to what active learning methods to use to prepare pharmacy graduates for this. Thus the review of worldwide literature occurred to be helpful in identifying what active learning methods are being used specifically in teaching aspects of pharmaceutical care. Methods: Three electronic databases: Pubmed, Scopus and Web of Science were searched using the keywords "active learning" and "pharmaceutical care". Results: On the basis of the publications included in the review, 7 methods were distinguished. Case-study, role play and simulation exercises turned out to be the most popular. It was also possible to make preliminary conclusions on how to properly match the method to the learning outcomes. Moreover, a weak point of many studies was the lack of structured methods of assessing the skills acquired by the students. Conclusions: In conclusion, the curriculum renewal in pharmacy is necessary and requires taking many aspects into account, from the types of tasks assigned to pharmacists, through the selection of appropriate teaching methods, to the verification of assessment methods.

Microneedle-based ocular drug delivery systems - recent advances and challenges.

Eye diseases and injuries constitute a significant clinical problem worldwide. Safe and effective delivery of drugs to the eye is challenging mostly due to the presence of ocular barriers and clearance mechanisms. In everyday practice, the traditional eye drops, gels and ointments are most often used. Unfortunately, they are usually not well tolerated by patients due to the need for frequent use as well as the discomfort during application. Therefore, novel drug delivery systems with improved biopharmaceutical properties are a subject of ongoing scientific investigations. Due to the developments in microtechnology, in recent years, there has been a remarkable advance in the development of microneedle-based systems as an alternative, non-invasive form for administering drugs to the eye. This review summarizes the latest achievements in the field of obtaining microneedle ocular patches. In the manuscript, the most important manufacturing technologies, microneedle classification, and the research studies related to ophthalmic application of microneedles are presented. Finally, the most important advantages and drawbacks, as well as potential challenges related to the unique anatomy and physiology of the eye are summarized and discussed.

Towards the Preparation of a Hydrogel from Lyophilisates of the Aloe arborescens Aqueous Extract.

Aloe gel is a medicinal raw material with proven pharmacological activity. The health-promoting properties of other species of Aloe upon topical application prompted us to develop a formulation for the topical application of A. arborescence species. As a result of the gel preparation from the aqueous lyophilized extracts of three-year-old leaves of A. arborescence, no changes in the composition of the content of aloins A and aloenin A were found. The potential to neutralize free radicals was tested using DPPH and CUPRAC techniques, which confirmed the anti-radical activity of the lyophilisate. Screening of the inhibition of enzymes, the hyperactivity of which is associated with adverse changes in the skin of a pro-inflammatory nature, was performed. Importantly, using the PAMPA SKIN model, the possibility of the penetration of selected extract compounds (aloin A and aloenin A) through the skin was proven. Then, two formulations were prepared based on sodium alginate and hydroxypropyl methylcellulose (HPMC) and the hydrogels were characterized (rheological analysis, drug release profiles, permeability, and stability studies). HPMC-based hydrogel was the one with a targeted release of active substances and greater stability. Aloe arborescens hydrogel matrices seem to be a promising treatment strategy for inflammatory surface damage based on "green technology" at the stage of extract preparation and development of the drug form for topical application.

Polish Pharmacy Students' Attitudes toward Undergraduate Teaching and Practical Implementation of Pharmaceutical Care-A Cross Sectional Study.

It is necessary to monitor and adapt pharmacy curricula to make graduates ready to effectively meet the health needs of the society. Therefore, the aim of the study was to obtain Polish final year pharmacy students' opinions on the activities related to pharmaceutical care (PC) andtheir perception of PC. Two questionnaires were used: one evaluating a PC regarding classes and in practice (n = 64), and the other on the assessment of existing educational solutions in the field of professional counseling (n = 118). Statistical analysis showed that the students agreed that there are not enough hours of a PC classes, since these are necessary to enable them to provide PC services in the future (R = 0.05, p = 0.0007). In previous classes, teachers' knowledge was rated the highest on a five-point scale (4.74), and role play (3.92) and the duration of the classes (3.77) were rated the lowest. Although the students were aware of the role of a PC in the work of a pharmacist, they indicated that more extensive use of active learning methods would better prepare them for the profession. Therefore, pharmacy students' self-efficacy survey and a curriculum renewal would be recommended in Poland.

Rheological and textural analysis as tools for investigation of drug-polymer and polymer-polymer interactions on the example of low-acyl gellan gum and mesalazine.

PURPOSE: In the performed study, the rheological and textural parameters of gellan-based hydrogels were investigated and their dependence on three factors was taken into consideration: (i) The presence of the model drug, (ii) The presence and type of the ionic crosslinking agent, and (iii) the composition of the polymer network. The objective was to compare two analytical methods, regarded as complementary, and define to what extent the obtained results correlate with each other. METHODS: The hydrogels contained low-acyl gellan gum or its mixtures with hydroxyethyl cellulose or κ-carrageenan. CaCl2 and MgCl2 were used as gelling agents. Mesalazine was used as a model drug. The rheological analysis included oscillatory stress and frequency sweeping. The texture profile analysis was performed to calculate texture parameters. RESULTS: Placebo gels without the addition of gelling agents had the weakest structure. The drug had the strongest ability to increase the stiffness of the polymer network. The weakest structure revealed the placebo samples without the addition of gelling agents. Texture analysis revealed no significant influence of the drug on the strength of the gels, while rheological measurements indicated clear differences. CONCLUSIONS: It can be concluded that in the case of some parameters methods correlate, that is, the effect related to gelling ions. However, the rheological analysis seems to be more precise and sensitive to some changes in the mechanical properties of the gels.

Ionotropic Gelation and Chemical Crosslinking as Methods for Fabrication of Modified-Release Gellan Gum-Based Drug Delivery Systems.

Hydrogels have a tridimensional structure. They have the ability to absorb a significant amount of water or other natural or simulated fluids that cause their swelling albeit without losing their structure. Their properties can be exploited for encapsulation and modified targeted drug release. Among the numerous natural polymers suitable for obtaining hydrogels, gellan gum is one gaining much interest. It is a gelling agent with many unique features, and furthermore, it is non-toxic, biocompatible, and biodegradable. Its ability to react with oppositely charged molecules results in the forming of structured physical materials (films, beads, hydrogels, nanoparticles). The properties of obtained hydrogels can be modified by chemical crosslinking, which improves the three-dimensional structure of the gellan hydrogel. In the current review, an overview of gellan gum hydrogels and their properties will be presented as well as the mechanisms of ionotropic gelation or chemical crosslinking. Methods of producing gellan hydrogels and their possible applications related to improved release, bioavailability, and therapeutic activity were described.

Development and Evaluation of Thermosensitive Hydrogels with Binary Mixture of Scutellariae baicalensis radix Extract and Chitosan for Periodontal Diseases Treatment.

Scutellaria baicalensis root displays anti-inflammatory and antibacterial properties due to the presence of flavonoids, particularly baicalin, baicalein, and wogonin. Our work aimed at developing thermosensitive hydrogels containing a binary mixture of S. baicalensis radix lyophilized extract and chitosan as a novel approach for periodontal diseases treatment. Two types of chitosan were employed in preliminary studies on binary mixtures with S. baicalensis radix lyophilized extract standardized for baicalin, baicalein, and wogonin. Thermosensitive hydrogels were prepared of poloxamer 407, alginate sodium, and cellulose derivatives and evaluated in terms of rheological and mucoadhesive behavior. The presence of chitosan altered the release profile of active compounds but did not affect their in vitro permeation behavior in PAMPA assay. The synergistic effects of S. baicalensis radix lyophilized extract and chitosan toward ferrous ion-chelating activity, inhibition of hyaluronidase, and pathogen growth were observed. The thermosensitive gelling system showed shear-thinning properties, gelation temperature between 25 and 27 °C, and favorable mucoadhesiveness in contact with porcine buccal mucosa, which was enhanced in the presence of binary mixture of S. baicalensis radix extract and chitosan. The release tests showed that baicalin and baicalein were liberated in a prolonged manner with a fast onset from hydrogel formulations.

Recent Advances in Polymer-Based Vaginal Drug Delivery Systems.

The vagina has been considered a potential drug administration route for centuries. Most of the currently marketed and investigated vaginal formulations are composed with the use of natural or synthetic polymers having different functions in the product. The vaginal route is usually investigated as an administration site for topically acting active ingredients; however, the anatomical and physiological features of the vagina make it suitable also for drug systemic absorption. In this review, the most important natural and synthetic polymers used in vaginal products are summarized and described, with special attention paid to the properties important in terms of vaginal application. Moreover, the current knowledge on the commonly applied and innovative dosage forms designed for vaginal administration was presented. The aim of this work was to highlight the most recent research directions and indicate challenges related to vaginal drug administrations. As revealed in the literature overview, intravaginal products still gain enormous scientific attention, and novel polymers and formulations are still explored. However, there are research areas that require more extensive studies in order to provide the safety of novel vaginal products.

Microemulsion-Based Media in Nose-to-Brain Drug Delivery.

Nose-to-brain drug delivery has recently attracted enormous attention as an alternative to other delivery routes, including the most popular oral one. Due to the unique anatomical features of the nasal cavity, drugs administered intranasally can be delivered directly to the central nervous system. The most important advantage of this approach is the ability to avoid the blood-brain barrier surrounding the brain and blocking the entry of exogenous substances to the central nervous system. Moreover, selective brain targeting could possibly avoid peripheral side effects of pharmacotherapy. The challenges associated with nose-to-brain drug delivery are mostly due to the small volume of the nasal cavity and insufficient drug absorption from nasal mucosa. These issues could be minimized by using a properly designed drug carrier. Microemulsions as potential drug delivery systems offer good solubilizing properties and the ability to enhance drug permeation through biological membranes. The aim of this review is to summarize the current status of the research focused on microemulsion-based systems for nose-to-brain delivery with special attention to the most extensively investigated neurological and psychiatric conditions, such as neurodegenerative diseases, epilepsy, and schizophrenia.

Deformable Liposomal Hydrogel for Dermal and Transdermal Delivery of Meloxicam.

BACKGROUND AND AIM: Meloxicam (MX) is a potent hydrophobic non-steroidal anti-inflammatory drug used to reduce inflammation and pain. However, its oral dosage form can cause many adverse gastrointestinal effects. In the present study, a poloxamer P407 based hydrogel system containing transfersomes or flavosomes has been prepared as a potential therapeutic vehicle for the topical delivery of MX. METHODS: In this study, MX was encapsulated in conventional liposomes, transfersomes, and flavosomes. The obtained liposomal vesicles were characterized in terms of size, drug entrapment efficiency, zeta potential, and stability. These MX-loaded liposomal formulations were further incorporated into a poloxamer P407 gel and evaluated using rheological properties, a stability study and an ex vivo permeation study through human cadaver skin by both HPLC analysis and confocal laser scanning microscopy (CLSM). RESULTS: The developed deformable liposomes exhibited homogeneous vesicle sizes less than 120 nm with a higher entrapment efficiency as compared to conventional liposomes. The deformable liposomal gel formulations showed improved permeability compared to a conventional liposomal gel and a liposome-free gel. The enhancement effect was also clearly visible by CLSM. CONCLUSION: These deformable liposomal hydrogel formulations can be a promising alternative to conventional oral delivery of MX by topical administration. Notably, flavosome-loaded gel formulations displayed the highest permeability through the deeper layers of the skin and shortened lag time, indicating a potential faster on-site pain relief and anti-inflammatory effect.