Advanced Formulation Approaches for Proteins.

Proteins and peptides are highly desirable as therapeutic agents, being highly potent and specific. However, there are myriad challenges with processing them into patient-friendly formulations: they are often unstable and have a tendency to aggregate or degrade upon storage. As a result, the vast majority of protein actives are delivered parenterally as solutions, which has a number of disadvantages in terms of cost, accessibility, and patient experience. Much work has been undertaken to develop new delivery systems for biologics, but to date this has led to relatively few products on the market. In this chapter, we review the challenges faced when developing biologic formulations, discuss the technologies that have been explored to try to overcome these, and consider the different delivery routes that can be applied. We further present an overview of the currently marketed products and assess the likely direction of travel in the next decade.

Using simulation to improve pharmacy operators' handling of cytotoxic spills.

INTRODUCTION: International Society of Oncology Pharmacy Practitioners guidelines recommend having standard operating procedures (SOPs) and initial and yearly retraining programs on cytotoxic spill handling for pharmacy operators (POs). This study aimed to create a simulation-based training (SBT) program on this subject and evaluate its impact on POs' real-life performance. METHODS: Randomly formed pairs of POs underwent a 2.5-hour training program, including two simulation exercises (a broken cytotoxic vial on the floor and a leaking cytotoxic bag) in a simulated pharmacy production unit. Each participant applied the cytotoxic spill handling SOPs. The PO and trainer-pharmacist did a debriefing after each exercise. Satisfaction was recorded on a 0-to-100% scale. A 20-item questionnaire assessed general knowledge about cytotoxic spill handling before and after the training. One month before and one month after the training, the POs underwent a real-life test when the trainer broke a fake cytotoxic vial in the cytotoxic storage area. Their performance in applying the SOPs was assessed on a 20-point checklist, and the time to handle the spill was recorded. RESULTS: Twelve POs participated. Mean satisfaction score was 98.9%. Mean knowledge score improved from 10.8/20 (SD = 2.0) before training to 14.5/20 (SD = 1.6) after training (p < 0.05). Mean real-life SOP performance improved from 78.6% (SD = 7.4%) to 97.1% (SD = 5.2%) (p < 0.05). Mean time to handle cytotoxic spills decreased from 17.3 minutes (SD = 3.6 minutes) to 11.9 minutes (SD = 1.5 minutes) (p < 0.05). CONCLUSION: POs improved their knowledge and real-life competencies for handling cytotoxic spills. This training will be included in POs' initial and continuing training programs.

Lemongrass essential oil micro- and nanoencapsulation for industrial application: Production techniques and potential applications.

Due to its characteristic aroma and diverse therapeutic properties, lemongrass essential oil (LEO) has garnered increased attention in the pharmaceutical, food, and cosmetic industries. However, LEO's volatile nature, low chemical stability, and limited solubility in water limits its applications in the industry. Micro- and nanoencapsulation technologies emerge as a promising solution to overcome these challenges. A systematic methodology involving keyword searches in databases was employed to gather relevant literature on LEO micro- and nanoencapsulation, providing an extensive overview of techniques, processes, encapsulating materials, and possible applications. Beyond established methods, emerging techniques were explored. This review highlights the critical role of encapsulation in enhancing the thermal and chemical stability, applicability, bioavailability, and controlled release of LEO.

[Overwiew of compounding oncology pharmacy in France in 2021]. / États des lieux de la pharmacotechnie oncologique en France en 2021.

The pharmacotechnical expert group of the French Society of Oncological Pharmacy presents the results of its national survey carried out in 2021 in the form of an inventory of pharmaceutical compounding units dedicated to oncology. Premises, equipment, controls, production flows and trends are described in this article, providing an overview of the sector at a time when the new Good Manufacturing Practices (GMP) are applicable. This overview will allow us to better address the needs and expectations of production pharmacists regarding the application of GMP and the development of their units.

Game-based learning as training to use a chemotherapy preparation robot.

INTRODUCTION: In 2015, our university hospital pharmacy acquired the PharmaHelp robot system to automate part of its chemotherapy production. Complex technical use, downtime periods, and insufficient training caused a drop in motivation and disparities in operators' knowledge. We created a short, playful, standardized, gamed-based training program to address this, and evaluated its impact. METHODS: Operators were classified as trainers or trainees according to their knowledge about Information and Communication Technologies. Before, after the training, and at 6 months (6M), their robot knowledge was assessed on a 0-24-scale, motivation and self-efficacy in using it on 0-to-100 scales. Pairwise comparison t-test with Bonferroni adjustment was used (p < 0.05 considered significant). Satisfaction was measured using a six-point Likert scale. Trainer/trainee teams participated in 2-hour training sessions with three games and a debriefing. For "Knowing the manufacturing steps," cards with the steps were placed in the correct order. For "Knowing the criteria for using the robot," teams guessed whether certain compounds could be used with the robot. For "Knowing how to handle production errors," the answer to each error (taken from real-life issues) was selected from four options. RESULTS: Participants (n = 14) were very satisfied about sessions' interactivity and playfulness. Knowledge improved from 57% pretraining to 77% (p < 0.005) to 76.6% (6M) (p < 0.05 compared to pretraining). Motivation and self-efficacy, respectively, improved from 57.6% to 86.6% (p < 0.05) to 70.4% (6M) and from 48.5% to 75.6% (p < 0.05) to 60.2% (6M) (p > 0.1 compared to pretraining) (t-test). CONCLUSIONS: This highly appreciated training program efficiently improved knowledge retention out to six months.

Stakeholder perspectives on cooperation in the clinical and nonclinical health technology assessment domains.

OBJECTIVES: The aim of this study was to deliver insights from multiple stakeholders into actual and future collaboration for health technology assessment (HTA) in general and in oncology in particular. METHODS: Eighteen semi-structured interviews were conducted with experts from European HTA bodies (HTAbs), former board members of the European Network for Health Technology Assessment (EUnetHTA), and representatives from the pharmaceutical industry, a regulatory agency, academia, and patient organizations. The stakeholders were asked about their support of the EUnetHTA's intent, about the general strengths and challenges of the EUnetHTA and its Joint Action 3 (JA 3), the strengths and challenges of the clinically oriented HTA collaboration in oncology during JA 3 across the technology life cycle, about future challenges to HTA in oncology with consequences for collaboration, and about collaboration in the economic domains of HTA. The transcribed interviews were analyzed qualitatively. RESULTS: The participants perceived the intention and work quality of the EUnetHTA as positive. The experts described methodological, procedural, and capacity challenges in early dialogues (EDs) and rapid relative effectiveness assessments (REAs) meant to analyze clinical effectiveness in oncology. The majority attached increasing importance to collaboration in the future to cope with the uncertainty of HTA. Several stakeholders also proposed the incorporation of joint postlaunch evidence generation (PLEG) activities. Some gave sporadic suggestions for voluntary nonclinical collaboration as well. CONCLUSION: Stakeholders' continued readiness to discuss the remaining challenges to and sufficient resources for implementing HTA regulation, as well as further cooperative expansion along the technology life cycle, are necessary for improved HTA collaboration in Europe.

Topical formulation containing chitosan-chamomile microparticles in cutaneous wound healing in rats.

Objective: The aim of this research was to evaluate the efficacy of a topical formulation containing chitosan-chamomile microparticles in cutaneous healing in rats. Method: Male Wistar rats (n=57) were randomly distributed into three groups: treatment; vehicle; and control. Evaluations were performed on days 2, 7 and 14 after the surgical procedure using skin lesion photography, and histological and biochemical analyses. Results: The results showed that there was no difference in the healing index and in the histological analysis of the inflammatory infiltrate among groups. Fibrogenesis was more significant in the group treated with the test formulation at day 7, and angiogenesis was greater in the vehicle and chamomile groups at day 2. The quantification of hydroxyproline showed a higher amount of collagen in the group treated with chamomile, mainly at day 14, although the histological quantification of collagen showed no difference between the groups. Conclusion: From the results of this study, it can be concluded that the formulation, although it had no effect on the healing time, improved the quality of the cicatricial tissue formed with a greater quantity of fibroblasts and collagen.

Direct Compaction Drug Product Process Modeling.

Most challenges during the development of solid dosage forms are related to the impact of any variations in raw material properties, batch size, or equipment scales on the product quality and the control of the manufacturing process. With the ever pertinent restrictions on time and resource availability versus heightened expectations to develop, optimize, and troubleshoot manufacturing processes, targeted and robust science-based process modeling platforms are essential. This review focuses on the modeling of unit operations and practices involved in batch manufacturing of solid dosage forms by direct compaction. An effort is made to highlight the key advances in the past five years, and to propose potentially beneficial future study directions.

ACTUALITIES IN ENDOCRINE PHARMACOLOGY: ADVANCES IN THE DEVELOPMENT OF ORAL FORMULATIONS FOR CALCITONIN AND SEMAGLUTIDE.

As the medical utility of injectable therapeutic peptides is expanding, so is the challenge of developing technologies that allow the administration of such molecules via alternative routes, considering that chronic patients requiring treatment with parenteral formulations are less adherent and compliant to the therapeutic regimens. Hence, substantial efforts have been made to develop technologies that allow the oral formulation of peptides. Due to their importance in the field of pharmaceutical technology, we describe the latest advancements made in the development of oral salmon calcitonin and oral semaglutide, in co-formulation with absorption enhancers such as 8-[(5-chloro-2-hydroxybenzoyl) amino] octanoic acid (or 5-CNAC) and N-[8-(2-hydroxybenzoyl) amino] caprylate (or SNAC). Oral semaglutide is considered to be a landmark for oral peptide delivery technology, as it is one of the very few successful examples of peptides that can be administered orally. Unlike semaglutide, oral calcitonin is still not approved by the regulatory authorities because it failed to demonstrate the anticipated effects in phase III clinical trials conducted so far. However, the efforts for obtaining an oral form of calcitonin have significantly contributed to the development of technologies that facilitate the absorption of peptide-structure macromolecules.

Cyclodextrin⁻Drug Inclusion Complexes: In Vivo and In Vitro Approaches.

This review aims to provide a critical review of the biological performance of natural and synthetic substances complexed with cyclodextrins, highlighting: (i) inclusion complexes with cyclodextrins and their biological studies in vitro and in vivo; (ii) Evaluation and comparison of the bioactive efficacy of complexed and non-complexed substances; (iii) Chemical and biological performance tests of inclusion complexes, aimed at the development of new pharmaceutical products. Based on the evidence presented in the review, it is clear that cyclodextrins play a vital role in the development of inclusion complexes which promote improvements in the chemical and biological properties of the complexed active principles, as well as providing improved solubility and aqueous stability. Although the literature shows the importance of their ability to help produce innovative biotechnological substances, we still need more studies to develop and expand their therapeutic properties. It is, therefore, very important to gather together evidence of the effectiveness of inclusion complexes with cyclodextrins in order to facilitate a better understanding of research on this topic and encourage further studies.

[Pharmaceutical system of fecal microbiota transplantation: Heterogeneous practices]. / Circuit pharmaceutique, transplantation de microbiote fécal : Des pratiques hétérogènes.

OBJECTIVE: To describe current pharmaceutical practice in French hospitals regarding fecal microbiota transplantation in terms of prescription, preparation and compounding, as well as local legislation. MATERIAL AND METHODS: A national survey was conducted at 28 French university hospital centers followed by the sending of a GoogleForm® questionnaire from June to August 2018 in the 16 respondent centers either performing or subcontracting fecal microbiota transplant. RESULTS: All hospitals performing or subcontracting fecal transplant (n=16,%57) report prescription indication of recurrent Clostridium difficile infection treatment, and 6 of them also as part of a clinical trial protocol. In hospitals performing fecal transplant themselves (n=11), the number of pre-donation consultations with donors varies from one (n=6) to two (n=5). Fecal sample is collected at the donor's home in 45% of cases. Route of administration for transplant is either naso-gastric administration (n=4), rectal (n=4) or both (n=5). Fecal samples for transplant are compounded either in the hospital pharmacy (n=73%) or in the laboratory (27%). Thawing methods include refrigeration between 2-8°C (50%), room temperature (25%) and water bath (25%). Billing system and reporting to health authorities are highly heterogeneous from one hospital to another. CONCLUSION: This survey shows significant pharmaceutical practice heterogeneity within French hospitals regarding fecal microbiota transplantation despite the existence of national and European recommendations.

[Intelligent and lean manufacturing for Chinese medicine:theory and its applications].

To cope with the " six major scientific problems" and the " five major technical challenges" of intelligent manufacturing and lean production of Chinese medicine( CM),we systematically proposed strategies,methods and the engineering theory of intelligent and lean manufacturing for CM by integrating the holistic view of traditional Chinese medicine and the concepts inspired from international advanced pharmaceutical technology. Moreover,the translational research of the theory and methods was successfully applied to six CMs such as Xuesaitong Injection. Several intelligent production lines were designed and built on the basis of the theory and methods,which greatly accelerated the digitalization,networking,and intelligence manufacture for CM. As a conclusion,the theory and applications provide technical demonstration for technical upgrading and high-quality development of CM industry.

The Impact of the National Institute for Pharmaceutical Technology and Education on Academic Research.

Surveys of institutional representatives of member institutions and faculty members engaged in the National Institute for Pharmaceutical Technology and Education (NIPTE) revealed that NIPTE is having a positive impact on academic research in the area of pharmaceutical technology by aligning research directions with FDA needs, by providing funding that may not be available elsewhere, and by creating a collegial and collaborative relationship among researchers in this area from various institutions. NIPTE is contributing to the viability of pharmaceutics and pharmaceutical engineering research in academic settings. Some responders cite the fluctuations in funding and relative low levels of funding received as a problem in maintaining programs, but most perceived a positive impact.

Novel topical formulation for ischemic chronic wounds. Technological design, quality control and safety evaluation.

Ulceration of the foot in diabetes is common and disabling, and frequently leads to amputation of the leg. The pathogenesis of foot ulceration is complex, clinical presentation variable and management requires early expert assessment. Despite treatment, ulcers readily become chronic wounds. Chronic wounds are those that remain in a chronic inflammatory state failing a normal healing process patterns. This is partially caused by inefficient eradication of opportunistic pathogens like Pseudomonas aeruginosa. We propose its control or eradication will promote wound healing. Lactobacillus plantarum cultures supernatants (LAPS) shows antipathogenic and pro-healing properties. The main objective was to design two pharmaceutical dosage forms by using LAPS as active pharmaceutical ingredient and to perform its quality control, in vitro activity conservation tests and human trials (safety evaluation). Both selected formulations reach the technological quality expected for 120 days, shows adequate occlusive characteristics and proper adhesion to human skin. From the in vitro release assays were found that LAPS shows adequate release from matrix and maintain its antimicrobial and anti-biofilm activity. First human trials were developed and neither edema nor erythema on healthy skin voluntaries was found. We conclude that C80 and C100 are adequate for their use in future clinical trials to demonstrate a comprehensive therapeutic effectiveness in ischemic chronic wounds.

[Chinese medicine industry 4.0：advancing digital pharmaceutical manufacture toward intelligent pharmaceutical manufacture].

A perspective analysis on the technological innovation in pharmaceutical engineering of Chinese medicine unveils a vision on "Future Factory" of Chinese medicine industry in mind. The strategy as well as the technical roadmap of "Chinese medicine industry 4.0" is proposed, with the projection of related core technology system. It is clarified that the technical development path of Chinese medicine industry from digital manufacture to intelligent manufacture. On the basis of precisely defining technical terms such as process control, on-line detection and process quality monitoring for Chinese medicine manufacture, the technical concepts and characteristics of intelligent pharmaceutical manufacture as well as digital pharmaceutical manufacture are elaborated. Promoting wide applications of digital manufacturing technology of Chinese medicine is strongly recommended. Through completely informationized manufacturing processes and multi-discipline cluster innovation, intelligent manufacturing technology of Chinese medicine should be developed, which would provide a new driving force for Chinese medicine industry in technology upgrade, product quality enhancement and efficiency improvement.

Nanocellulose, the Green Biopolymer Trending in Pharmaceuticals: A Patent Review.

The use of nanocellulose in pharmaceutics is a trend that has emerged in recent years. Its inherently good mechanical properties, compared to different materials, such as its high tensile strength, high elastic modulus and high porosity, as well as its renewability and biodegradability are driving nanocellulose's industrial use and innovations. In this sense, this study aims to conduct a search of patents from 2011 to 2023, involving applications of nanocellulose in pharmaceuticals. A patent search was carried out, employing three different patent databases: Patentscope from World Intellectual Property Organization (WIPO); Espacenet; and LENS.ORG. Patents were separated into two main groups, (i) nanocellulose (NC) comprising all its variations and (ii) bacterial nanocellulose (BNC), and classified into five major areas, according to their application. A total of 215 documents was retrieved, of which 179 were referred to the NC group and 36 to the BNC group. The NC group depicted 49.7%, 15.6%, 16.2%, 8.9% and 9.5% of patents as belonging to design and manufacturing, cell culture systems, drug delivery, wound healing and tissue engineering clusters, respectively. The BNC group classified 44.5% of patents as design and manufacturing and 30.6% as drug delivery, as well as 5.6% and 19.4% of patents as wound healing and tissue engineering, respectively. In conclusion, this work compiled and classified patents addressing exclusively the use of nanocellulose in pharmaceuticals, providing information on its current status and trending advancements, considering environmental responsibility and sustainability in materials and products development for a greener upcoming future.

Knowledge and Perception of Pharmacy Students toward Telepharmacy Education in Saudi Arabia.

Telepharmacy education should be incorporated into the curricula due to its beneficial effects on students, providing pharmacy services during their practice. Therefore, this study aims to explore the knowledge and perceptions of pharmacy students regarding the integration of telepharmacy services into their education curriculum in Saudi Arabia. A cross-sectional study was conducted using an online survey from 1 June to 30 September 2023, among pharmacy students from five universities in Saudi Arabia. The questionnaire was divided into three sections, and descriptive statistics and a generalized linear model were used for analysis. A total of 523 pharmacy students participated. Approximately half of the students were aware of telepharmacy, and only one-quarter had studied it as part of their curriculum. Students believed that telepharmacy education should cover communication, reimbursement, and training for virtual patient interactions. There was a significant positive correlation (p < 0.0001) between the knowledge and perception scores. In addition, students who had heard about telepharmacy before and those with a "somewhat" confidence level showed a significantly positive correlation with knowledge scores (p = 0.01). In conclusion, perception scores, students who had heard of telepharmacy, and those with a "somewhat" confidence level were all positively correlated with pharmacy students' understanding of telepharmacy. This study underscores the importance of integrating telepharmacy education and practical training into pharmacy curricula to prepare future pharmacists for the evolving healthcare landscape.

New Horizons in Antiretroviral Drug Delivery Systems for HIV Management

INTRODUCTION: Human Immunodeficiency Virus (HIV) infection is still a major global problem, whose drug treatment consists of prophylactic prevention and antiretroviral combination therapy for better pharmacological efficacy and control of the circulating virus. However, there are still pharmacological problems that need to be overcome, such as low aqueous solubility of drugs, toxicity, and low patient adherence. Drug delivery technologies can be used to overcome these barriers. OBJECTIVE: This review summarized the latest drug delivery systems for HIV treatment. Initially, an overview of the current therapy was presented, along with the problems it presents. Then, the latest drug delivery systems used to overcome the challenges imposed in conventional HIV therapy were discussed. CONCLUSION: This review examines innovative approaches for HIV treatment, where various drug delivery systems have shown significant advantages, such as high drug encapsulation, improved solubility, and enhanced bioavailability both in vitro and in vivo. Strategies like cyclodextrins, solid dispersions, microneedles, and nanoparticles are explored to address challenges in drug solubility, bioavailability, and administration routes. Despite progress, obstacles like limited clinical trials and industrial scalability hinder the widespread adoption of these formulations, emphasizing the need for further research and collaboration to optimize and ensure accessibility of innovative HIV therapies, mainly in regions where access to HIV treatment is scarce and remains a challenge.

An automated dispensing cabinet alert influences anesthesia provider medication preparation in a remifentanil waste reduction initiative.

STUDY OBJECTIVE: To decrease the occurrence of remifentanil waste of 1 mg or more (1 full vial) by 25 % in our surgical division while maintaining satisfaction of 60 % of providers by using a remifentanil mixing workflow. DESIGN: A time series-design quality improvement initiative targeted preventable remifentanil waste. A period of active interventions, followed by a pause and reinstatement of a system intervention, was used to validate its effectiveness. SETTING: An academic medical center in the US with 1219 inpatient beds, performing 144,418 surgical cases in 2019 and 127,341 surgical cases in 2020, in 148 operating rooms. INTERVENTIONS: Individual- and system-level interventions provided education on the issues of preventable waste, access to a remifentanil dose calculator, and an automated dispensing cabinet (ADC) alert to halt wasteful practice. MEASUREMENTS: Preventable remifentanil waste was identified as disposing of intravenous infusion bags containing 1 mg or more or 1 full vial or more of unused medication. Data were retrieved from ADC reports. A preimplementation and postimplementation survey of anesthesia providers assessed workflow attitudes, perceptions, and satisfaction surrounding remifentanil mixing. MAIN RESULTS: Preventable remifentanil waste (≥1 mg or ≥ 1 full vial) decreased significantly from 22.0 % of cases using remifentanil at baseline to 16.7 % of cases using remifentanil (odds ratio, 0.71; 95 % CI, 0.60-0.84; P < .001) during the final data collection. Individual-level interventions of education, remifentanil dose calculator, and practice champions did not significantly affect waste while unpaired from the system intervention of the ADC alert. CONCLUSIONS: The implementation of an ADC alert reduced preventable remifentanil waste among anesthesia providers.

Peptide GLP-1 receptor agonists: From injection to oral delivery strategies.

Peptide glucagon-like peptide-1 receptor agonists (GLP-1RAs) are effective drugs for treating type 2 diabetes (T2DM) and have been proven to benefit the heart and kidney. Apart from oral semaglutide, which does not require injection, other peptide GLP-1RAs need to be subcutaneously administered. However, oral semaglutide also faces significant challenges, such as low bioavailability and frequent gastrointestinal discomfort. Thus, it is imperative that advanced oral strategies for peptide GLP-1RAs need to be explored. This review mainly compares the current advantages and disadvantages of various oral delivery strategies for peptide GLP-1RAs in the developmental stage and discusses the latest research progress of peptide GLP-1RAs, providing a useful guide for the development of new oral peptide GLP-1RA drugs.