Cysteamine Eye Drops in Hyaluronic Acid Packaged in Innovative Single-Dose Systems, Part II: Long-Term Stability and Clinical Ocular Biopermanence.

BACKGROUND: Cystinosis is a rare genetic disorder characterized by the accumulation of cystine crystals in several tissues and organs causing, among others, severe eye symptoms. The high instability of cysteamine eye drops makes it difficult to develop formulations with an acceptable shelf life to be prepared in hospital pharmacy departments. Previously, a new compounded formulation of cysteamine eye drops in hyaluronic acid (HA) packaged in innovative single-dose systems was developed. METHODS: Long-term stability at -20 °C of this formulation was studied considering the content of cysteamine, pH, osmolality, viscosity, and microbiological analysis. The oxygen permeability of single-dose containers was also studied and an ocular biopermanence study was conducted in healthy volunteers measuring lacrimal stability and volume parameters. RESULTS: Data confirm that cysteamine concentration remained above 90% for 120 days, all parameters remaining within the accepted range for ophthalmic formulations. The permeability of the containers was reduced over time, while ocular biopermanence was maintained despite the freezing process and storage time. CONCLUSIONS: 0.55% cysteamine hydrochloride formulation in HA and packaged in single-dose containers preserved at -20 °C is stable for 120 days protected from light, presenting high potential for its translation into clinical practice when commercial presentations are not available.

TELEA-Farmacia: Pharmaceutical care by Telepharmacy to oncology patients from a hospital pharmacy service.

OBJECTIVE: To describe the implementation of a pilot Telepharmacy project (TELEA-Farmacia) in adult patients with cancer, analyze the results obtained, and identify opportunities for improvement, from a hospital  pharmacy service. METHOD: Between October and December 2021, oncology patients, collecting  their oral antineoplastic drugs at the Unit of Oncology Pharmacy of the hospital pharmacy service were stratified using the MAPEX model. Oncology patients  candidates for inclusion in the TELEA-Farmacia project included "medium-high  priority" hospital pharmacy patients, along with oncology patients who,  according to pharmacist's opinion, could benefit from Telepharmacy. On a  weekly basis, oncology patients recorded on the TELEA platform their biological  measurements and completed the questionnaires on medication  adherence and pain. Questionnaires on quality of life were completed on a  monthly basis. To score health indicators, oncology patients accessed TELEA  through the SERGAS-MOBIL app or a web browser. Follow-up of health  indicators was performed by the Unit of Oncology Pharmacy of the hospital  pharmacy service. RESULTS: The study sample included 29 oncology patients (48% were male)  with a mean age of 59 years (44-75). According to the stratification model,  31% were low-priority patients, 62% had medium-priority, and 7%  had high  priority. The digital gap in patients with advanced ages was the main obstacle  to inclusion. Reports were monitored daily, and a total of 364 responses were  received. In the presence of alarming reports and/or out-of-range values,  active monitoring and/or telephonic follow-up were initiated. Pharmaceutical  care was adapted to the health problem detected according to individual  patient needs. CONCLUSIONS: The Telemedicine pilot project TELEA-Farmacia made it possible  to test TELEA in patients with cancer in a real-life context. TELEA facilitated  continuous follow-up, early detection of drug-related problems, and the  identification of new needs and improvement points. To such purpose, clinical  oncology pharmacists combined face-to-face consults with patient stratification  and remote follow-up. This study demonstrated that new  stratification models are necessary in hospital pharmacy services to identify  patients with technology skills who can benefit from using Telemedicine tools  as TELEA.

OBJETIVO: Describir la implantación de un proyecto piloto de Telefarmacia (TELEA-Farmacia) en el paciente oncológico adulto y analizar los resultados recabados, así como identificar las oportunidades de mejora, desde un servicio de farmacia hospitalario.Método: Entre octubre y diciembre de 2021, los pacientes oncológicos a  tratamiento con antineoplásicos orales citados en la consulta de farmacia oncológica del servicio de farmacia de hospital fueron estratificados a  través del modelo MAPEX. Se consideraron susceptibles de inclusión en TELEA- Farmacia a quienes requerían atención farmacéutica con "prioridad media-alta" y a aquellos que, según criterio farmacéutico, pudieran beneficiarse de la herramienta. A través del aplicativo TELEA se programaron semanalmente biomedidas y cuestionarios de adherencia y evaluación del  dolor, y mensualmente un cuestionario de calidad de vida. Accediendo a TELEA  mediante la aplicación móvil SERGAS-MÓBIL o un navegador web, los  pacientes oncológicos respondieron a los indicadores de salud programados, de cuyo seguimiento fue responsable la Unidad de Farmacia Oncológica del  servicio de farmacia de hospital. RESULTADOS: Se incluyeron 29 pacientes oncológicos (48% hombres), con una  media de 59 años (44-75). Un 31% fueron de prioridad baja, 62% media y 7%  alta según el modelo de estratificación, siendo la brecha digital existente  en edades avanzadas el principal impedimento para la inclusión. Se realizó un  seguimiento diario de las notificaciones, recibiéndose un total de 364  respuestas. A partir de las consideradas alarmantes y de los valores fuera de  rango, se procedió al seguimiento activo y/o contacto telefónico,  proporcionando atención farmacéutica adaptada al problema de salud  detectado en función de las necesidades. CONCLUSIONES: El proyecto piloto de Telemedicina TELEA-Farmacia permitió testar la herramienta en pacientes oncológicos en vida real, facilitando el seguimiento continuado, la detección temprana de problemas  relacionados con medicamentos y la identificación de nuevas necesidades y  puntos de mejora para su implantación definitiva en la actividad asistencial.  Para ello, fue necesario compaginar la actividad presencial en consulta con el tiempo requerido para la estratificación y seguimiento telemático. Además, ha evidenciado la necesidad de disponer de nuevos modelos de  estratificación en un servicio de farmacia de hospital para la atención  farmacéutica que contemplen el manejo de las tecnologías por parte de los  pacientes, para identificar así a quienes más se puedan beneficiar de la  herramienta de Telemedicina TELEA.

Cysteamine Eye Drops in Hyaluronic Acid Packaged in Innovative Single-Dose Systems: Stability and Ocular Biopermanence.

Cystinosis is a rare genetic disorder characterized by the accumulation of cystine crystals in different tissues and organs causing, among other symptoms, severe ocular manifestations. Cysteamine eye drops are prepared in hospital pharmacy departments to facilitate access to treatment, for which vehicles that provide adequate biopermanence, as well as adaptable containers that maintain its stability, are required. Difficulties related to cysteamine preparation, as well as its tendency to oxidize to cystamine, show the importance of conducting rigorous galenic characterization studies. This work aims to develop and characterize an ophthalmic compounded formulation of cysteamine prepared with hyaluronic acid and packaged in innovative single-dose systems. For this task, the effect of different storage temperatures and the presence/absence of nitrogen on the physicochemical stability of the formulation and its packaging was studied in a scaled manner, until reaching the optimal storage conditions. The results showed that 0.55% cysteamine, prepared with hyaluronic acid and packaged in single-dose containers, is stable for 30 days when stored at -20 °C. In addition, opening vials every 4 h at room temperature after 30 days of freezing maintains the stability of the cysteamine formulation for up to 16 h. Moreover, ocular biopermanence studies were conducted using molecular imaging, concluding that the biopermanence offered by the vehicle is not affected by the freezing process, where a half-life of 31.11 min for a hyaluronic acid formulation stored for 30 days at -20 °C was obtained, compared with 14.63 min for 0.9% sodium chloride eye drops.

Current Situation and Challenges in Vitreous Substitutes.

Vitreo-retinal disorders constitute a significant portion of treatable ocular diseases. These pathologies often require vitreo-retinal surgery and, as a consequence, the use of vitreous substitutes. Nowadays, the vitreous substitutes that are used in clinical practice are mainly divided into gases (air, SF6 , C2 F6 , C3 F8 ) and liquids (perfluorocarbon liquids, silicone oils, and heavy silicone oils). There are specific advantages and drawbacks to each of these, which determine their clinical indications. However, developing the ideal biomaterial for vitreous substitution continues to be one of the most important challenges in ophthalmology, and a multidisciplinary approach is required. In this sense, recent research has focused on the development of biocompatible, biodegradable, and injectable hydrogels (natural, synthetic, and smart), which also act as medium and long-term internal tamponade agents. This comprehensive review aims to cover the main characteristics and indications for use of the extensive range of vitreous substitutes that are currently used in clinical practice, before going on to describe the hydrogels that have been developed recently and which have emerged as promising biomaterials for vitreous substitution.

Recent Research in Ocular Cystinosis: Drug Delivery Systems, Cysteamine Detection Methods and Future Perspectives.

Cystinosis is a rare genetic disorder characterized by the accumulation of cystine crystals in different tissues and organs. Although renal damage prevails during initial stages, the deposition of cystine crystals in the cornea causes severe ocular manifestations. At present, cysteamine is the only topical effective treatment for ocular cystinosis. The lack of investment by the pharmaceutical industry, together with the limited stability of cysteamine, make it available only as two marketed presentations (Cystaran® and Cystadrops®) and as compounding formulations prepared in pharmacy departments. Even so, new drug delivery systems (DDSs) need to be developed, allowing more comfortable dosage schedules that favor patient adherence. In the last decades, different research groups have focused on the development of hydrogels, nanowafers and contact lenses, allowing a sustained cysteamine release. In parallel, different determination methods and strategies to increase the stability of the formulations have also been developed. This comprehensive review aims to compile all the challenges and advances related to new cysteamine DDSs, analytical determination methods, and possible future therapeutic alternatives for treating cystinosis.