Special Issue "Advance in Development of Patient-Centric Dosage Form"

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Physical Pharmacy and Formulation".

Deadline for manuscript submissions: 30 September 2022 | Viewed by 10428

Special Issue Editors

Dr. Laura Modica de Mohac
E-Mail Website
Guest Editor
Institute of Pharmaceutical Science, King’s College London, London SE19NH , UK
Interests: medicine acceptability; patient-centric formulation; sustained release dosage form; solid dosage form
Prof. Dr. Dimitrios A. Lamprou
E-Mail Website
Co-Guest Editor
School of Pharmacy, Queen’s University Belfast, Belfast BT9 7BL, UK
Interests: 3D printing; bioprinting; drug delivery; electrospinning; medical devices; pharmaceutics; microfluidics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

It is established that the medication acceptability of dosage forms could influence patient compliance and treatment efficacy and safety. Currently, research focuses on developing patient-centric formulations as personalized dosage forms where the product provides the benefits for individual patient needs. According to the World Health Organization (WHO), patient-centric formulations are becoming essential for public health when dealing with long-term diseases treated with multiple drugs. However, data related to the understanding of dosage form-related issues in medication acceptability are lacking. Therefore, the development of advanced technologies has resulted in significant efforts to develop customizable dosage forms.

The focus of this Special Issue of Pharmaceutics will be on assessing and identifying dosage form-related issues in medication acceptability and recent advances in the development of effective strategies to produce patient-centric dosage forms to improve acceptability. This Special Issue will accept both Reviews and Research articles.

Dr. Laura Modica de Mohac
Dr. Dimitrios A. Lamprou
Guest Editors

Manuscript Submission Information

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Keywords

  • medication acceptability
  • patient-centric dosage forms
  • solid dosage forms
  • assessment
  • advance
  • technology
  • product customization

Published Papers (10 papers)

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Research

Article
Are There Differences in the Homogeneity of the Parts of Tablets Obtained after Subdivision?—A Preliminary Assessment Using an X-ray Microtomography
Pharmaceutics 2022, 14(9), 1850; https://doi.org/10.3390/pharmaceutics14091850 - 01 Sep 2022
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Abstract
Aim: The study aimed to analyze the weight and homogeneity of the parts of tablets containing carbamazepine and tablets with trazodone hydrochloride, obtained after subdivision with a kitchen knife. X-ray microtomography was used for homogeneity analysis. Methods: 30 tablets with carbamazepine and 30 [...] Read more.
Aim: The study aimed to analyze the weight and homogeneity of the parts of tablets containing carbamazepine and tablets with trazodone hydrochloride, obtained after subdivision with a kitchen knife. X-ray microtomography was used for homogeneity analysis. Methods: 30 tablets with carbamazepine and 30 tablets with trazodone hydrochloride were analyzed in terms of weight uniformity after subdivision. Then, seven tablets of each type were analyzed using an X-ray microtomography (Phoenix vǀtomeǀx, General Electric). The absorption of X-rays by an object is proportional to its density. In turn, measurement of the density of the analyzed object in a microtomographic image is the grayscale level. Based on the correlation between the grayscale value and the reference density, from the calibration phantom, we were able to determine the density of any area of the tablet’s scan. Results: During the subdivision, the weight loss exceeded 3% for two carbamazepine tablets, while for trazodone tablets, none lost more than 3%, which is the limit recommended by Food and Drug Administration (FDA). As to the density of the tablets resulting from the microtomographic analysis, two of the whole tablets containing trazodone hydrochloride had a significantly higher density than the remainder (p < 0.001). Similarly, some differences in density were observed in the analysis of the density of tablets of carbamazepine (p = 0.008). Parts of one of the analyzed tablets with trazodone obtained after subdivision differed in terms of pixel brightness, thus density. On the other hand, the uniform density was observed for parts of the split tablets containing carbamazepine. Conclusions: Parts of the trazodone hydrochloride tablets obtained after subdivision differed in terms of homogeneity and weight. Microtomographic methods may be an interesting and useful method for evaluating the uniformity of compounds in solid dosage forms. Full article
(This article belongs to the Special Issue Advance in Development of Patient-Centric Dosage Form)
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Article
Formulation Development of Fluconazole-Loaded Lactose Agglomerate Tablets as a Disinfectant for Candida-Associated Dentures
Pharmaceutics 2022, 14(8), 1723; https://doi.org/10.3390/pharmaceutics14081723 - 18 Aug 2022
Viewed by 345
Abstract
Denture stomatitis is induced by irritation or an inflammatory response when wearing a denture for a long time. Candida species are the leading cause of biofilm formation on the surfaces and fissures of dentures. Thus, this study aimed to formulate and evaluate fluconazole [...] Read more.
Denture stomatitis is induced by irritation or an inflammatory response when wearing a denture for a long time. Candida species are the leading cause of biofilm formation on the surfaces and fissures of dentures. Thus, this study aimed to formulate and evaluate fluconazole tablets for use in preparing a disinfectant mixture with anticandidal activity. For size enlargement of lactose, a tablet diluent, using polyvinylpyrrolidone (PVP) as an agglomerating agent, was developed to enhance the flowability and compactability of the tablet preparation using direct compression. Lactose agglomerates with 6% PVP were used as a diluent for the fluconazole tablets. Furthermore, other excipients were used, such as a buffering agent, disintegrant, surfactant, and lubricant. The fluconazole tablets obtained could be dispersed and dissolved within 10 min in distilled water to achieve a clear mixture, providing a neutral pH and 96% transmittance. Furthermore, the fluconazole mixtures displayed anticandidal efficiency against C. albicans with a similar effect to the standard fluconazole solution. These findings suggest that the fluconazole-loaded lactose agglomerate tablets show strong potential when prepared using direct compression. The fluconazole mixtures made by dispersing the tablets can be used as a disinfectant for Candida-associated dentures, particularly in patients with oral candidiasis. Full article
(This article belongs to the Special Issue Advance in Development of Patient-Centric Dosage Form)
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Article
Gastro-Resistant Microparticles Produced by Spray-Drying as Controlled Release Systems for Liposoluble Vitamins
Pharmaceutics 2022, 14(7), 1480; https://doi.org/10.3390/pharmaceutics14071480 - 15 Jul 2022
Viewed by 451
Abstract
In the present study, gastro-resistant microparticles (MPs) were produced using the spray-drying technique as controlled-release systems for some model liposoluble vitamins, including retinyl-palmitate, retinyl-acetate, β-carotene, cholecalciferol and α-tocopherol. The gastroprotective action of three different gastro-resistant excipients, the anionic methacrylic copolymer (Eudraguard®® Biotic, [...] Read more.
In the present study, gastro-resistant microparticles (MPs) were produced using the spray-drying technique as controlled-release systems for some model liposoluble vitamins, including retinyl-palmitate, retinyl-acetate, β-carotene, cholecalciferol and α-tocopherol. The gastroprotective action of three different gastro-resistant excipients, the anionic methacrylic copolymer (Eudraguard®® Biotic, E1207), the cellulose acetate phthalate (CAP) and whey proteins (WPs), was compared. The latter was used to produce a novel delivery system manufactured with only food-derived components, such as milk, and showed several improvements over the two synthetic gastro-resistant agents. Scanning electron microscopy (SEM) images showed a quite homogeneous spherical shape of all microparticle batches, with an average diameter between 7 and 15 μm. FTIR analysis was used to evaluate the effective incorporation of vitamins within the microparticles and the absence of any degradation to the components of the formulation. The comparison graphs of differential scanning calorimetry (DSC) confirmed that the spray drying technique generates a solid in which the physical interactions between the excipients and the vitamins are very strong. Release studies showed a prominent pH-controlled release and partially a delayed-release profile. Ex vivo permeation studies of retinyl palmitate, retinyl acetate and α-tocopherol revealed greater transmucosal permeation capacity for microparticles produced with the WPs and milk. Full article
(This article belongs to the Special Issue Advance in Development of Patient-Centric Dosage Form)
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Article
Swallowability of Minitablets among Children Aged 6–23 Months: An Exploratory, Randomized Crossover Study
Pharmaceutics 2022, 14(1), 198; https://doi.org/10.3390/pharmaceutics14010198 - 15 Jan 2022
Cited by 1 | Viewed by 559
Abstract
Minitablets have garnered interest as a new paediatric formulation that is easier to swallow than liquid formulations. In Japan, besides the latter, fine granules are frequently used for children. We examined the swallowability of multiple drug-free minitablets and compared it with that of [...] Read more.
Minitablets have garnered interest as a new paediatric formulation that is easier to swallow than liquid formulations. In Japan, besides the latter, fine granules are frequently used for children. We examined the swallowability of multiple drug-free minitablets and compared it with that of fine granules and liquid formulations in 40 children of two age groups (n = 20 each, aged 6–11 and 12–23 months). We compared the percentage of children who could swallow minitablets without chewing with that of children who could swallow fine granules or liquid formulations without leftover. The children who visited the paediatric department of Showa University Hospital were enrolled. Their caregivers were allowed to choose the administration method. In total, 37 out of 40 caregivers dispersed the fine granules in water. Significantly more children (80%, 95% CI: 56–94%) aged 6–11 months could swallow the minitablets than those who could swallow all the dispersed fine granules and liquid formulations (22%, 95% CI: 6–47% and 35%, 95% CI: 15–59%, respectively). No significant differences were observed in children aged 12–23 months. Hence, minitablets may be easier to swallow than dispersed fine granules and liquid formulations in children aged 6–11 months. Full article
(This article belongs to the Special Issue Advance in Development of Patient-Centric Dosage Form)
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Article
Exploring Acceptability Drivers of Oral Antibiotics in Children: Findings from an International Observational Study
Pharmaceutics 2021, 13(10), 1721; https://doi.org/10.3390/pharmaceutics13101721 - 18 Oct 2021
Cited by 2 | Viewed by 1352
Abstract
Antibiotics are among the most commonly prescribed drugs in children. Adherence to the treatment with these drugs is of the utmost importance to prevent the emergence of resistant bacteria, a global health threat. In children, medicine acceptability is likely to have a significant [...] Read more.
Antibiotics are among the most commonly prescribed drugs in children. Adherence to the treatment with these drugs is of the utmost importance to prevent the emergence of resistant bacteria, a global health threat. In children, medicine acceptability is likely to have a significant impact on compliance. Herein we used a multivariate approach, considering simultaneously the many aspects of acceptability to explore the drivers of oral antibiotic acceptability in children under twelve, especially in toddlers and in preschoolers. Based on 628 real-life observer reports of the intake of 133 distinct medicines, the acceptability reference framework highlighted the influence of many factors such as age and sex of patients, previous exposure to treatment, place of administration, administration device, flavor agent in excipients and active pharmaceutical ingredient. These findings from an international observational study emphasize the multidimensional nature of acceptability. Therefore, it is crucial to consider all these different aspects for assessing this multi-faceted concept and designing or prescribing a medicine in order to reach adequate acceptability in the target population. Full article
(This article belongs to the Special Issue Advance in Development of Patient-Centric Dosage Form)
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Article
Tablet Splitting in Elderly Patients with Dementia: The Case of Quetiapine
Pharmaceutics 2021, 13(9), 1523; https://doi.org/10.3390/pharmaceutics13091523 - 20 Sep 2021
Cited by 2 | Viewed by 1359
Abstract
Quetiapine is an atypical antipsychotic approved for treating schizophrenia, bipolar depression, and mania but is frequently used in an off-label manner to control the behavioral and psychological symptoms of dementia in elderly patients with dementia. Due to the need to personalize doses for [...] Read more.
Quetiapine is an atypical antipsychotic approved for treating schizophrenia, bipolar depression, and mania but is frequently used in an off-label manner to control the behavioral and psychological symptoms of dementia in elderly patients with dementia. Due to the need to personalize doses for elderly patients with dementia, quetiapine tablet manipulation is widespread in hospital settings, long-term care facilities, and patient homes. The aim of this study was to assess the impact of the different splitting techniques on quetiapine fumarate tablets by analysing the obtained sub-divided tablets and to discuss compliance with the European Pharmacopoeia limits on whole and split tablets. Quetiapine fumarate tablets of two dose strengths were taken at random (in a number able to assure a power of 0.8 during statistical comparison) and were split with a kitchen knife or tablet cutter. The weight and the drug content were determined for each half tablet. The obtained data were compared to the European Pharmacopoeia limits. The differences between the different splitting techniques were statistically tested. Data showed that split tablets, independently of the dose strength and the technique employed, were not compliant with the European Pharmacopoeia specifications for both entire and subdivided tablets in terms of weight and content uniformity. Thus, such a common practice could have potential effects on treatment efficacy and toxicity, especially when also considering the fragility of the elderly target population in which polypharmacotherapy is very common. These results indicate a compelling need for flexible quetiapine formulations that can assure more accurate dose personalization. Full article
(This article belongs to the Special Issue Advance in Development of Patient-Centric Dosage Form)
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Article
Formulation Development of Sublingual Cyclobenzaprine Tablets Empowered by Standardized and Physiologically Relevant Ex Vivo Permeation Studies
Pharmaceutics 2021, 13(9), 1409; https://doi.org/10.3390/pharmaceutics13091409 - 06 Sep 2021
Cited by 2 | Viewed by 866
Abstract
Suitable ex vivo models are required as predictive tools of oromucosal permeability between in vitro characterizations and in vivo studies in order to support the development of novel intraoral formulations. To counter a lack of clinical relevance and observed method heterogenicity, a standardized, [...] Read more.
Suitable ex vivo models are required as predictive tools of oromucosal permeability between in vitro characterizations and in vivo studies in order to support the development of novel intraoral formulations. To counter a lack of clinical relevance and observed method heterogenicity, a standardized, controlled and physiologically relevant ex vivo permeation model was established. This model combined the Kerski diffusion cell, process automation, novel assays for tissue integrity and viability, and sensitive LC-MS/MS analysis. The study aimed to assess the effectiveness of the permeation model in the sublingual formulation development of cyclobenzaprine, a promising agent for the treatment of psychological disorders. A 4.68-fold enhancement was achieved through permeation model-led focused formulation development. Here, findings from the preformulation with regard to pH and microenvironment-modulating excipients proved supportive. Moreover, monitoring of drug metabolism during transmucosal permeation was incorporated into the model. In addition, it was feasible to assess the impact of dosage form alterations under stress conditions, with the detection of a 33.85% lower permeation due to salt disproportionation. Integrating the coherent processes of disintegration, dissolution, permeation, and metabolization within a physiological study design, the model enabled successful formulation development for cyclobenzaprine sublingual tablets and targeted development of patient-oriented drugs for the oral cavity. Full article
(This article belongs to the Special Issue Advance in Development of Patient-Centric Dosage Form)
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Article
Stability of Hydrocortisone in Oral Powder Form Compounded for Pediatric Patients in Japan
Pharmaceutics 2021, 13(8), 1267; https://doi.org/10.3390/pharmaceutics13081267 - 17 Aug 2021
Cited by 1 | Viewed by 879
Abstract
Hydrocortisone has been utilized in the management of adrenal insufficiency. For pediatric patients, the commercially available enteral form of hydrocortisone tablets (Cortoril®) is administered in powder form after being compounded by a pharmacist. However, the stability and quality of compounded hydrocortisone [...] Read more.
Hydrocortisone has been utilized in the management of adrenal insufficiency. For pediatric patients, the commercially available enteral form of hydrocortisone tablets (Cortoril®) is administered in powder form after being compounded by a pharmacist. However, the stability and quality of compounded hydrocortisone powder have not been verified. In this study, we formulated a 20 mg/g oral hydrocortisone powder by adding lactose monohydrate to crushed and filtered hydrocortisone tablets and assessed the stability and physical properties of this compounded product in polycarbonate amber bottles or coated paper packages laminated with cellophane and polyethylene. Stability was examined over 120 days in three storage conditions: closed bottle, in-use bottle, and laminated paper. Drug dissolution and powder X-ray diffraction analysis were conducted to assess its physicochemical stabilities. Validated liquid chromatography-diode array detection was used to detect and quantify hydrocortisone and its degradation products. Although impurity B (cortisone) and G (hydrocortisone-21-aldehyde) were found after 120 days of storage, no crystallographic and dissolution changes were noted. Hydrocortisone content was maintained between 90% and 110% of initial contents for 120 days at 25 ± 2 °C and 60 ± 5% relative humidity in all packaging conditions. Full article
(This article belongs to the Special Issue Advance in Development of Patient-Centric Dosage Form)
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Article
Accuracy of Dose Administered to Children Using Off-Labelled or Unlicensed Oral Dosage Forms
Pharmaceutics 2021, 13(7), 1014; https://doi.org/10.3390/pharmaceutics13071014 - 02 Jul 2021
Cited by 1 | Viewed by 950
Abstract
The pediatric population suffers from a lack of age-appropriate medicines leading to unsafe situations when off-labelled or unlicensed drugs are used. Assessing the best option to administrate medicines when manipulations are required is essential in order to improve child care. This study aimed [...] Read more.
The pediatric population suffers from a lack of age-appropriate medicines leading to unsafe situations when off-labelled or unlicensed drugs are used. Assessing the best option to administrate medicines when manipulations are required is essential in order to improve child care. This study aimed to compare the accuracy of the administered dose provided by three dosage forms and their techniques of administration. Different techniques of administration were assessed, covering three oral dosage forms (commercially available tablets, capsules, oral suspensions) using two APIs not available in a children-adapted dosage form. Techniques of administration were simulated and administered doses were determined using HPLC-UV. Means were compared to the target dose while distributions of doses were compared between each technique. For both APIs, mean administered doses obtained with capsules and tablets were significantly different from the target dose, whereas there was no statistical difference with oral suspensions. Distributions of doses showed significant difference between the three dosage forms. This study demonstrates that manipulations of solid oral dosage forms provide dramatic underdosing leading to unsafe situations. Compounded oral suspension is the best option to avoid underdosing and dose variation. This solution should be prioritized when age-appropriate commercial medicines are not available. Full article
(This article belongs to the Special Issue Advance in Development of Patient-Centric Dosage Form)
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Article
Functionality and Acceptance of the EsoCap System—A Novel Film-Based Drug Delivery Technology: Results of an In Vivo Study
Pharmaceutics 2021, 13(6), 828; https://doi.org/10.3390/pharmaceutics13060828 - 02 Jun 2021
Cited by 3 | Viewed by 1498
Abstract
There are no methods for specific local application of active substances to the mucosa of the esophagus to treat eosinophilic esophagitis or other esophageal diseases. This publication describes the principal in vivo functionality and acceptance of a novel modular drug delivery concept, called [...] Read more.
There are no methods for specific local application of active substances to the mucosa of the esophagus to treat eosinophilic esophagitis or other esophageal diseases. This publication describes the principal in vivo functionality and acceptance of a novel modular drug delivery concept, called EsoCap system, by 12 healthy volunteers. For the first time, the EsoCap system enables targeted placement on the esophageal mucosa of a mucoadhesive polymer film. Acceptance was determined by means of a standardized questionnaire after administration and functionality of the device by MRI scans. Two different setups of the EsoCap system were tested: one setup with a density of 0.4 g/cm3 and one with a density of 1.0 g/cm3. Acceptability of the dosage form was also confirmed in addition to functionality, by measuring the applied film length. It was found that acceptance of the variant with the higher density was significantly better. This novel drug delivery technology could enable a targeted, local and long-lasting therapy of the esophagus for the first time, depending on the polymer film used. Full article
(This article belongs to the Special Issue Advance in Development of Patient-Centric Dosage Form)
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