A simple and rapid spectrophotometric method for the determination of trans-chalcone in raw-materialand topical formulation / Método espectrofotométrico simples e rápido paradeterminação de trans-chalcona em matéria-primae em formulação tópica

Trans-chalcone (TC) is a flavonoid precursor characterized by a wide spectrum of action, with anti-inflammatory and antioxidant effects. However, no validated methods are available in official compendia for the analysis of this substance. Thus, the aim of this work was to develop and validate a simple, fast, and reproducible spectrophotometric method for the analysis of TC in raw material, and in topical pharmaceutical formulation containing TC. The established conditions were: methanol as extracting solvent, and detection wavelength of 309 nm by UV spectrophotometer. All tests followed the rules of Resolution RDC 166, 2017. The proposed method was selective. Linearity was demonstrated in the concentration range of 1 to 8 µg/mL (r = 0.999). Repeatability and intermediate precision were confirmed by low relative standard deviation values of 1.53% and 2.70% for TC, and of 1.73% and 2.91% for formulation containing TC. Accuracy, evaluated through recovery test, was adequate, with minimum of 98.24% and maximum of 100.23% of recovery. It was observed that the small deliberate modifications done did not interfere with the results, demonstrating the method is robust. The results showed that the method was considered suitable for the intended purpose, inexpensive, easy to apply, selective, linear, precise, accurate, and robust for the determination TC, and pharmaceutical formulation containing TC. Thus, the method developed satisfies the need for an analytical method for the determination of TC, and topical formulation containing TC, being effective, innovative and able to aid in the development of the pharmaceutical field.

Trans-chalcona (TC) é um precursor de flavonoides caracterizado por um amplo espectro de ação, como efeitos anti-inflamatórios e antioxidantes. No entanto, não há método validado disponível em compêndio oficial para análise deste composto. Então, o objetivo deste trabalho foi desenvolver e validar um método espectrofotométrico, simples, rápido e reprodutível para análise de TC em matéria-prima, e em formulação farmacêutica tópica contendo TC. As condições estabelecidas foram: metanol como o solvente de extração, e detecção no comprimento de onda de 309 nm por espectrofotometria no UV. Todos os testes seguiram as normas da RDC 166, 2017. O método proposto foi seletivo. A linearidade foi demonstrada na faixa de concentração de 1 a 8 µg/mL (r = 0.999). A repetibilidade e a precisão intermediária foram confirmadas pelos valores baixos de desvio padrão relativo de 1,53% e 2,70% para a TC, e de 1,73% e 2,91% para a formulação contendo TC. A exatidão, avaliada por meio de testes de recuperação, foi adequada, com mínimo de 98,24% e máximo de 100,04% de recuperação. Observou-se que pequenas modificações no método não interferiram nos resultados, demonstrando que o método é robusto. Os resultados demonstraram que o método foi adequado para a finalidade pretendida, barato, de fácil aplicação, seletivo, linear, preciso, exato e robusto para determinação de TC, e de formulação contendo TC. Então o método desenvolvido satisfaz as necessidades de um método analítico para determinação de TC, e de formulação tópica contendo TC, e é eficaz, inovador e pode contribuir para o desenvolvimento da área farmacêutica.

Polyvinyl alcohol-chitosan based oleanolic acid nanofibers against bacterial infection: In vitro studies and in vivo evaluation by optical and laser Doppler imaging modalities.

The present work focuses on the fabrication of polyvinyl alcohol-chitosan-loaded oleanolic acid-nanofibers (PVA-CS-OLA-NFs) for bacterial infection. The prepared PVA-CS-OLA-NFs were characterized for contact angle, SEM, AFM, XRD, FTIR, and TGA. The solid-state characterization and in vitro performance evaluation of nanofibers reveal consistent interconnection and diameters ranging from 102 ± 9.5 to 386 ± 11.6 nm. The nanofibers have a flat surface topography and exhibit efficient drug entrapment. Moreover, the in vitro release profile of PVA-CS-OLA-NFs was found to be 51.82 ± 1.49 % at 24 h. Furthermore, the hemocompatibility study showed that the developed PVA-CS-OLA-NFs are non-hemolytic to human blood. The PVA-CS-OLA-NFs demonstrate remarkable antibacterial capabilities, as evidenced by their MBC and MIC values, which range from 128 and 32 µg/mL, against the strains of S. aureus. The in-vivo fluorescence optical imaging showed the sustained PVA-CS-OLA-NFs release at the wound site infected with S. aureus for a longer duration of time. Moreover, the PVA-CS-OLA-NFs showed superior wound healing performance against S. aureus infected wounds compared to the marketed formulation. Further, the laser Doppler imaging system improved oxygen saturation, blood supply, and wound healing by providing real-time blood flow and oxygen saturation information.

Understanding Global Access to Topical Onychomycosis Therapy: A Systematic Review and Meta-Analysis.

INTRODUCTION: Equal access to medicines is crucial to ensuring public health, but access is difficult to measure, especially for infections where changes in infective species make treatment choices highly dynamic. This study investigated if the combination of infection prevalence with medicine efficacy and regulatory availability could access medicines access of topical onychomycosis medicines. METHODS: Two databases, PubMed and Web of Science, were used to identify relevant information published between 1990 and 2019. For the meta-analysis, human onychomycosis investigations using PCR analysis were included. Reviewers independently selected eligible articles, extracted data and assessed the study quality. A random-effects meta-analysis model with a Freeman-Tukey transformation was employed to the PCR data. For the meta-analysis, the global infection trends and regional differences in the infective organisms were determined. RESULTS: Of the 26 studies analysed, the PCR analysis in 18 studies confirmed onychomycosis in about half of the visually suspected cases (55%, CI 43%-67%). Across all 26 studies dermatophytes were the most prevalent infective organism (57%, CI 37%-76%), but a sub-group analysis showed yeasts predominated in females (31%, CI 0%-84%) (p < 0.0001), in fingernail infections (42%, CI 21%-65%) (p < 0.0001) and in arid countries (p < 0.0001). Combining these results with medicine efficacy data showed that residents from 83 of the 92 countries assessed (90%) could not access the most efficacious topical product, and 22% could not access any broad-spectrum agents. Countries in Africa had the poorest access to topical onychomycosis medicines. CONCLUSION: This study identified that access to effective topical products for onychomycosis is a global problem. This issue appeared to be due to under-representation of candida infections in pivotal clinical studies of topical onychomycosis products. A head-to-head multicentre study for topical efinaconazole or a novel broad spectrum topical agent is needed to help resolve these access problems. PROTOCOL REGISTRATION: PROSPERO-CRD42023464744.

Preparation and characterization of Esculetin loaded nanostructured lipid carriers gels for topical treatment of UV-induced psoriasis.

SIGNIFICANCE: As an inflammatory and autoimmune skin condition, psoriasis affects 2-3% of people worldwide. Psoriasis requires prolonged treatments with immunosuppressive medications which have severe adverse effects. Esculetin (Esc) is a natural medication that has been utilized for the treatment of psoriasis. OBJECTIVE: The goal of this work is to improve Esc's solubility by developing novel Esc nanostructured lipid carriers (NLCs) for treating psoriasis and increase the residence time on skin which infer better skin absorption. METHODS: The particle size, zeta potential, and entrapment efficiency (EE) of Esc NLCs were assessed. Incorporating NLCs into gum Arabic gel preparation enhances their industrial applicability, absorption, and residence time on skin. Esc NLCs gels were evaluated by in vitro release and in vivo effectiveness on a rat model of UV-induced psoriasis. RESULTS: Esc NLCs showed high EE reaching more that 95% and reasonable particle size ranging between (53.86 ± 0.38 to 236.3 ± 0.11nm) and were spherical in shape. The release study of Esc NLCs gel demonstrated a fast release of Esc denoting enhanced bioavailability. In comparison to free Esc, Esc NLCs gel (F2) could considerably lower the level of CD34 and TNF-α in the skin. The results were validated through histopathological analysis. CONCLUSION: As Esc NLCs gel (F2) has strong anti-inflammatory properties, our results showed that it presented a significant potential for healing psoriasis.

Disease burden and patient characteristics associated with systemic therapy utilization among adults with atopic dermatitis: data from CorEvitas Atopic Dermatitis Registry.

BACKGROUND: The decision to initiate advanced systemics in patients with atopic dermatitis (AD) is complex. OBJECTIVES: To explore disease burden and clinical characteristics of patients with moderate-to-severe AD and identify characteristics associated with initiating new systemics. METHODS: Data from prospective, longitudinal, non-interventional CorEvitas AD Registry were evaluated. Differences in demographic and clinical characteristics, comorbidities, disease severity (vIGA-AD™; body surface area (BSA); Eczema Area and Severity Index (EASI); SCORing AD [SCORAD]), and patient-reported outcomes (PROs) were assessed between systemic and non-systemic therapy groups. RESULTS: Of 883 patients, 673 were newly prescribed systemics and 210 were not. Non-systemic therapy group had higher than expected rates of severe disease at enrollment based on vIGA-AD = 4 (39%), mean BSA involvement (31%), and mean EASI (19). PROs for non-systemic therapy group indicated elevated burden from AD on quality of life and poor disease control. SCORAD, peak pruritus in the past 24 h, history of biologics, and facial pallor, were significantly associated with initiation of systemics at enrollment. CONCLUSION: While disease burden likely influences the initiation of systemic therapy, many patients with significant burden are not treated with systemics for unclear reasons. Further research is needed to identify other factors, beyond disease severity, that influence this decision.

Microneedles as a potential platform for improving antibiotic delivery to bacterial infections.

Bacterial infections are mainly managed by the administration of antibiotics, which are either cytotoxic or cytostatic to microbes. In some cases, it is inconvenient to treat infections caused by bacteria using the traditional oral route for antibiotic administration. This can be due to the limited oral bioavailability of antibiotics, their gastrointestinal tract (GIT) adverse effects, and the increased possibility of the appearance of resistant strains. In addition, the fact that many populations are needle-phobic restricts the switch from the oral to the parenteral route. Furthermore, poor drug permeation throughout the stratum corneum of topically applied antibiotics causes low systemic bioavailability. Therefore, microneedles (MNs) have emerged as viable medicinal devices for the delivery of antibiotics, either for local or systemic effects. MNs represent a minimally invasive, painless way of administration that can be self-administered by the patient without the need of medical professionals. This review has specifically focused on MNs as a promising approach for the delivery of antibiotics; it has discussed the different types of MNs, their advantages, and possible limitations for the delivery of antibiotics. Recent studies on the incorporation of antibiotics into various types of MNs, either for topical or transdermal delivery are highlighted, and finally, we present the conclusion and future perspectives.

The Anaesthetic Efficacy of Tetracaine and Oxymetazoline Compared With Co-Phenylcaine in Healthy Individuals.

OBJECTIVES: Nasal anaesthetic-decongestant sprays are commonly used prior to nasal instrumentation, such as flexible and rigid nasal endoscopy. Co-phenylcaine (lignocaine 5%, phenylephrine 0.5%, ENT Technologies Pty Ltd., Melbourne, VIC, Australia) is a combination spray commonly used for this purpose. However, lignocaine is less potent than other local anaesthetics, and both active constituents of Co-phenylcaine have a bitter taste. It was hypothesised that a combination spray containing tetracaine and oxymetazoline would both offer more potent topical anaesthesia and have a better taste. METHODS: Four anaesthetic-decongestant nasal sprays were tested in 10 healthy participants (Co-phenylcaine, and tetracaine 0.5%, 1% and 2% with oxymetazoline 0.05%). Sensory thresholds were sequentially measured at the head of the inferior turbinate using Semmes-Weinstein monofilaments over the following hour. Participants also rated taste on a Likert-style scale, and reported whether they experienced subjective numbness of the maxillary teeth. RESULTS: A median peak sensory threshold of 60 g (the maximum tested) was observed with Co-phenylcaine, but this threshold was exceeded by all the tetracaine-based sprays. Tetracaine 2% with oxymetazoline 0.05% had a significantly more rapid onset than Co-phenylcaine (4 min vs. 6 min, p < 0.05) and a longer duration of action. Eight participants reported dental numbness after administration of tetracaine 2% with oxymetazoline 0.05%, but only one participant after Co-phenylcaine. Tetracaine-based sprays were generally perceived to taste less unpleasant than Co-phenylcaine. CONCLUSION: Tetracaine 2% with oxymetazoline 0.05% is a more potent and rapidly acting anaesthetic-decongestant spray than Co-phenylcaine, with a longer duration of action.

Fighting A New Front On An Old Battlefield: Examining the Development of Topical Antimicrobial Care to Control Burn Wound Sepsis.

Recognition of invasive burn wound sepsis as a major cause of morbidity and mortality in burn injured patients has profoundly changed the management of burn wounds and its associated complications. The development of effective topical antimicrobial therapy is one of the last major developments of modern burn care and has been driven by major world events and scientific breakthroughs. Topical antimicrobial burn care has evolved from the use of anecdotal remedies to scientific breakthroughs such as Moyer's successful dilution of silver nitrate solution, Fox's described benefit of silver sulfadiazine use in animal models, and Pruitt's dramatic improvement in post-burn mortality using topical mafenide acetate in burn wounds. The objective of this manuscript is to review the definition of burn wound sepsis and highlight the major developments and breakthroughs in topical burn wound care throughout history. This includes historical events like major wars or domestic fires that have influenced or impacted the understanding and treatment of burn wounds. Newer advances in topical antimicrobial care such as nanosilvers and dressing technologies that improve the morbidity and mortality associated with burn wound sepsis and novel approaches to management will also be discussed. To improve burn care, it is prudent to look to the past and learn from the experiences of those who contributed to the control of burn wound sepsis.

Skin-directed therapy and biologic response modifiers in mycosis fungoides.

The most common and widespread type of cutaneous T-cell lymphoma is mycosis fungoides (MF), and it has a multiphasic clinical and biological course, with early stages being indolent for many years and later stages being faster and more aggressive. The clinical stage has a significant impact on the management and course of treatment: in the early stages, skin-directed therapies (SDT) plus/or biologic response modifiers (BRM); in the later stages, radiotherapy and/or systemic therapies. Even though national and international societies and groups periodically update their clinical recommendations, there is still no universally accepted approach. This paper reviews and discusses the various SDT and BRM options, either separately or in combination.

Intravitreal injection practice patterns among Chinese ophthalmologists.

AIM: To describe the practice patterns of intravitreal injections (IVIs) among ophthalmologists in China. METHODS: This was a cross-sectional online survey. Ophthalmologists who had performed accumulated more than 100 injections were contacted by the Brightness Center, a hospital-based national network, to complete an anonymous, 24-question, internet-based survey. They were surveyed on practices in injection techniques, pre-, and post-injections procedures. RESULTS: A total of 333 ophthalmologists from 28 provinces/municipalities/autonomous regions responded to the survey (50.68% response rate). The 91.29% of the respondents evaluated systemic risk factors by medical history, electrocardiogram (ECG) and blood test. All the respondents used pre-injection prophylactic antibiotics. Most checked intraocular pressure (IOP, 99.1%) and blood pressure (96.1%) before injections. A majority of the respondents performed injections in the operating room (98.8%), wore masks (99.7%), gloves (99.4%) and sterile surgical clothing (96.1%), performed topical anesthetics (97.9%), and applied povidone-iodine (95.8%) pre-injection. The 61.26% of the respondents dilated pupil. About half of the respondents (51.05%) performed bilateral injections in the same setting. Superior temporal quadrant (40.54%) was the most frequent site of injection. Around three quarters used 30-gauge needles. Most respondents (97.9%) measured the site of injection from limbus. More than half (53.45%) performed conjunctiva displacement prior to injection. The 32.43% of the respondents checked IOP post-injection and 87.99% physicians checked hand motion (HM) or counting fingers (CF) after injection, while 36.94% observed optic nerve perfusion. All participants used topical antibiotics post-injections. Most physicians (91.89%) reviewed patients on the following day. CONCLUSION: This study provides a description of the real-world practice patterns in IVIs in China and offers critical information regarding education and training of ophthalmologists and amendment of local society guidelines.

Pregabalin-Induced Bullous Pemphigoid: A Case Report of a Rare Drug-Triggered Autoimmune Skin Disorder.

Bullous pemphigoid (BP) is a common autoimmune blistering disorder primarily affecting the elderly, characterized by intense pruritus and tense bullae on the skin. We report the case of a 75-year-old female with a history of breast cancer who developed BP on both feet following the initiation of pregabalin for pain management. Histopathological examination confirmed BP, and symptoms improved with topical corticosteroid treatment and discontinuation of pregabalin. This case highlights the potential of pregabalin to induce BP and underscores the importance of recognizing medication-induced bullous diseases for prompt diagnosis and management.

Development of gallic acid loaded composite nanovesicles for the topical treatment of acne: Optimization, Characterization, and Clinical investigation.

Gallic acid (GA) proved to produce desired effects topically in the treatment of acne, through its antibacterial, anti-inflammatory and antioxidant characteristics. In the current work, nanovesicular systems; aspasomes loaded with GA were prepared, and evaluated on in-vitro and ex-vivo levels. Formulations were coated with chitosan due to its mucoadhesive properties. Results indicated that the size of the formulations ranged between 273.20 and 855.00 nm, with positively charged zeta potential ranging between 30.60 and 34.40 mV, EE% ranging between 57.651% and 95.20% and good stability after 3-months storage. The formulae provided a sustained drug release of 98.22% over 24 h, 5.4-fold higher ex-vivo skin deposition compared to GA solution, and powerful antioxidant potential compared to the control solution and appeared as spherical bilayer vesicles on being examined using transmission electron microscope. A clinical study was carried out on patients suffering from acne, where the reduction percent of comedones, inflammatory, total acne lesions and infiltrate was calculated. Results revealed that aspasomes exhibited reduction percentages of 72.35%, 80.33%, 77.95% and 90.01% ± for comedones, inflammatory lesions, total lesions, and infiltrate, respectively compared to control solution providing an effective topical delivery system for the management of acne.

Performance of applications of Ophytrium-containing mousse with or without shampoo in cats with pruritic and irritated skin: a multicentre prospective field trial.

OBJECTIVES: This study aimed to evaluate the performance of a protocol in which topical products (DOUXO S3 CALM Shampoo and Mousse; Ceva Santé Animale) containing Ophytrium were applied to cats to help manage feline atopic syndrome (FAS). METHODS: A total of 23 client-owned cats with a history of FAS and presenting irritated skin and pruritus were recruited for this study. The cats were either shampooed or moussed on day 0 (D0) and then moussed every 48-72 h for 3 weeks. On D0, D7 and D21, clinical signs were assessed using the validated scoring system, Scoring Feline Allergic Dermatitis (SCORFAD). Pruritus was graded by the owner using an adapted dual visual analogue scale (Pruritus Visual Analog Scale for Cats [VAScat]). Veterinarians also assessed pruritus intensity and frequency, and provided a subjective assessment of global skin condition and of improvements in each cat's condition. On D21, all questionnaires were collected from both veterinarians and owners. RESULTS: Among the 19 cats that completed the study, the SCORFAD and VASmax (maximum value of VAScat, either scratching or licking) scores improved by ⩾50% in 63.2% and 38.9% of animals, respectively. Mean SCORFAD values decreased significantly between D0 and D21 (from 6.2 to 2.8, P <0.05). Similarly, mean VASmax values decreased significantly between D0 and D21 (from 7.4 to 4.3, P <0.05). Overall, veterinarians assessed the improvement as satisfactory, good or excellent in 18/19 (94.7%) cases. The protocol was considered efficient and practical by 18/19 (94.7%) and 19/19 (100%) owners, respectively, and the resulting good condition of skin and coat was emphasised by 15/19 (78.9%) owners. CONCLUSIONS AND RELEVANCE: This topical protocol with Ophytrium-containing mousse and shampoo was well tolerated. The products were effective in reducing skin irritation and discomfort quickly and significantly in cats with skin irritation and pruritus, yielding high satisfaction levels among both veterinarians and owners.

Topical Probiotic Hydrogels for Burn Wound Healing.

Hydrogels have increasingly been used to enhance the effective healing of various wounds, including burn wounds. Similarly, the application of probiotics has recently been explored in wound healing and skin repairs. While probiotics have been consumed to provide therapeutic effects that aid with improving gut health, topical applications have been found to accelerate wound healing both in vitro and in vivo. For wounds that have complex healing mechanisms, such as burn wounds which depend on factors such as the depth of the burn, size of the afflicted area, and cause of the injury, probiotics with or without conventional therapeutic agents topically delivered via hydrogel technology are proven to be effective in the recovery of the damaged skin. This article aims to investigate the microorganisms present in the human skin microbiome and observe the effects of probiotics delivered by hydrogels on burn wound healing.

Formulation and Evaluation of Turmeric- and Neem-Based Topical Nanoemulgel against Microbial Infection.

The combination of nanoemulgel and phytochemistry has resulted in several recent discoveries in the field of topical delivery systems. The present study aimed to prepare nanoemulgel based on turmeric (Curcuma longa) and neem (Azadirachta indica) against microbial infection as topical drug delivery. Olive oil (oil phase), Tween 80 (surfactant), and PEG600 (co-surfactant) were used for the preparation of nanoemulsion. Carbopol 934 was used as a gelling agent to convert the nanoemulsion to nanoemulgel and promote the control of the release of biological properties of turmeric and neem. The nanoemulsion was characterized based on particle size distribution, PDI values, and compatibility using FTIR analysis. In contrast, the nanoemulgel was evaluated based on pH, viscosity, spreadability, plant extract and excipient compatibility or physical state, in vitro study, ex vivo mucoadhesive study, antimicrobial properties, and stability. The resulting nanoemulsion was homogeneous and stable during the centrifugation process, with the smallest droplets and low PDI values. FTIR analysis also confirmed good compatibility and absence of phase separation between the oil substance, surfactant, and co-surfactant with both plant extracts. The improved nanoemulgel also demonstrated a smooth texture, good consistency, good pH, desired viscosity, ex vivo mucoadhesive strength with the highest spreadability, and 18 h in vitro drug release. Additionally, it exhibited better antimicrobial properties against different microbial strains. Stability studies also revealed that the product had good rheological properties and physicochemical state for a period of over 3 months. The present study affirmed that turmeric- and neem-based nanoemulgel is a promising alternative for microbial infection particularly associated with microorganisms via topical application.

Development and Investigation of a Nanoemulgel Formulated from Tunisian Opuntia ficus-indica L. Seed Oil for Enhanced Wound Healing Activity.

The aim of this study is to develop a nanoemulgel encapsulating a Tunisian Prickly Pear (Opuntia ficus-indica L.) seed oil (PPSO) to assess, for the first time, the in vivo efficacy of this nanoformulation on wound healing. Phytocompounds of this oil have been reported in the literature as having powerful pharmacological activities. However, it remains poorly exploited due to low bioavailability. A nanoemulsion (NE) was designed by determining the required hydrophilic-lipophilic balance (HLB) and subsequently characterized. The mean droplet size was measured at 56.46 ± 1.12 nm, with a polydispersity index (PDI) of 0.23 ± 0.01 using dynamic light scattering. The zeta potential was -31.4 ± 1.4 mV, and the morphology was confirmed and assessed using transmission electron microscopy (TEM). These characteristics align with the typical properties of nanoemulsions. The gelification process resulted in the formation of a nanoemulgel from the optimum nanoemulsion. The high wound healing efficiency of the nanoemulgel was confirmed compared to that of a medicinally marketed cream. The outcomes of this research contribute valuable insights, for the first time, into the potential therapeutic applications of PPSO and its innovative pharmaceutical formulation for wound healing.

Ayurvedic Management of Presbycusis (Project TOPMAC): Protocol for an Exploratory Randomized Controlled Trial.

BACKGROUND: Presbycusis is characterized by sensorineural hearing loss in both ears at high frequencies, which affects more than half of the older adults by the age of 75 years and is often accompanied by tinnitus and cognitive deterioration. Unfortunately, there are no treatments available to restore hearing loss. Treatment mainly focuses on improving the quality of life and communication with hearing aids. Traditional medicine like Ayurveda also explains ailments of a similar nature as Badhirya and advises using drugs with antiaging and neuroprotective activity for treatment. In Ayurveda, Badhirya and Karnanada (senile deafness with tinnitus) are due to vitiation of Vata Dosha. Treatments such as topical oil pooling (Karnapurana) are usually advised to counter Vata, improve hearing capacity, and reduce tinnitus. Kshirabala Taila, a medicated oil formulation prepared with Sida cordifolia Linnaeus, is one of the most preferred oils for topical oil pooling in such conditions, as it has a definitive indication for sensory dysfunctions. Drugs like Withania somnifera (L.) Dunal (Ashwagandha) are also used, as they ameliorate neurodegeneration and help to improve cognitive dysfunction. OBJECTIVE: We propose an exploratory randomized controlled trial study for evaluating the efficacy of TOPMAC (Topical Oil Pooling with Kshirabala Taila and Supplementation of Ashwagandha Churna) in tinnitus suppression and hearing and cognitive function protection in patients aged 60-75 years with mild to moderate presbycusis. METHODS: A parallel, 2-group, exploratory randomized controlled trial will be conducted in an Indian Ayurvedic research center at its outpatient service. Participants (N=60) with mild to moderate presbycusis will be recruited by screening. Participants will be randomized (computer-generated 1:1) to receive either basic treatment and health education (BTHE) or BTHE+TOPMAC for 24 weeks. The primary objective is to compare the efficacy of TOPMAC with that of BTHE in the protection of hearing function. The secondary objective is to compare the efficacy of TOPMAC with that of BTHE in tinnitus suppression and cognitive function protection. RESULTS: This project was funded in January 2023. The institutional ethics committees at National Ayurveda Research Institute for Panchakarma (3/1/2020/NARIP/Tech/2036) and Institute for Communicative and Cognitive Neuro Sciences (IEC006) approved this study. The first patient was enrolled in September 2023; 22 participants were enrolled as of August 2024. The data analysis is yet to start, and the results are expected to be published by January 2025. CONCLUSIONS: If this exploratory trial is proven effective, it will steer the setting of a definitive randomized controlled trial to test whether the TOPMAC intervention can be incorporated as a cost-effective integrative approach for managing presbycusis. The Indian government has already launched a National Program for Prevention and Control of Deafness to benefit the deaf population. TOPMAC may later be considered for integration with the national program. TRIAL REGISTRATION: Clinical Trials Registry India CTRI/2023/04/051485; https://tinyurl.com/2h2hry3n. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/55089.

Opportunities of topical drug products in a changing dermatological landscape.

Despite the prevalence and the impact on quality of life of dermatological indications, drug products to treat such conditions have rarely been blockbusters. The prevailing perception of a limited commercial potential of dermatological drug products has restricted innovation and encouraged a more conservative development approach. For example, the focus was on repurposing/reformulation of existing active pharmaceutical ingredients (APIs) specifically for the topical delivery route. However, the situation is quite different today catalyzed in part by the blockbuster success of Dupixent (dupilumab), the first monoclonal antibody treatment for atopic dermatitis which has been approved by the US Food and Drug Administration (US FDA) in 2017. Dupixent's success not only encouraged the development of other biologics but also inspired the (re-)development of new dermal drug products that can reap the many benefits of topical administration. We have also witnessed a shift toward outsourcing development efforts (and associated risks) towards small- to mid-size pharmaceutical companies which often require support of contract research and development/manufacturing organizations (CRO and CDMO). Such trends also emphasize the need of greater expertise in topical formulation design, as well as associated commercial and regulatory considerations. Today, we believe that topical drug products remain not only an essential but also commercially viable class of dermatological therapeutics. In this opinion article, we will address the challenges as well as opportunities of coherent development strategies in the current market environment, formulation innovations of topical drug products and technological advances to facilitate rational topical drug formulation development.

Topical treatment of chemotherapy-induced peripheral neuropathy (CIPN) with high-concentration (179 mg) capsaicin patch in breast cancer patients - results of the QUCIP study.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) following oral or intravenous chemotherapy often results in neuropathic pain, accompanied by symptoms such tingling, burning and hypersensitivity to stimuli, with a notable decline in quality of life (QoL). Effective therapies for CIPN are lacking, with a high demand for analgesics to address this issue. The QUCIP study aimed to assess the effectiveness of high concentration (179 mg) capsaicin patch (HCCP) in alleviating neuropathic pain and associated symptoms in breast cancer patients with confirmed CIPN. Methods: QUCIP is a prospective, multi-center observational study spanning 36 weeks with up to three HCCP treatments. Initial treatment (visit V0) was followed by two telephone contacts (T1, T2) and subsequent face-to-face visits every 12 weeks or upon retreatment (visits V1-V3). 73 female patients with painful CIPN post neoadjuvant/adjuvant breast cancer therapy were enrolled. Primary endpoint was the reduction of neuropathic pain symptom score (painDETECT®). Secondary endpoints included improvements in CIPN-specific QoL (QLQ-CIPN20), reductions in pain intensity (numeric pain rating scale, NPRS), and achievement of ≥ 30% and ≥ 50% pain reduction. Results: Median age was 61 years, with 52.0% of patients experiencing peripheral neuropathic pain for > 1 year (> 2 years: 34.2%). The painDETECT® score significantly decreased from baseline (19.71 ± 4.69) to 15.80 ± 6.20 after initial treatment (p < 0.0001) and continued to decrease at follow-up visits. The NPRS indicated significant pain intensity reduction at each time point, particularly pronounced in patients receiving three HCCP treatments. Clinically significant pain relief of ≥ 30% increased from 25.0% at week 4 (T2) to 36.2%, 43.5%, and 40.0% at weeks 12 (V1), 24 (V2), and 36 (V3), respectively. The percentage of patients achieving pain relief of ≥ 50% increased from 14.7% at T2 to 15.5%, 21.7% and 32.5% at V1, V2 and V3, respectively. Patients further reported a significant improvement in their CIPN-related QoL throughout the study. Adverse drug reactions (ADRs) mainly included application site reactions. Conclusion: In this study, HCCP shows benefit in managing CIPN in real-world settings. The data demonstrate a sustained and progressive reduction in neuropathic pain and symptomatology, confirming the clinical benefit of repeated treatment observed in former clinical trials. HCCP treatment has also the potential to significantly improve the QoL associated with CIPN. The safety profile of HCCP was confirmed, supporting its use in clinical practice.

Evaluation of pain associated with the application of burn dressings.

INTRODUCTION: Topical wound care after burn injury has revolutionized burn care. Dressings and topical solutions provide broad-spectrum antimicrobial coverage to prevent wound infection, be easy to apply and remove, and promote wound healing. A wide variety of dressings are available for providers to choose from based on wound characteristics. An additional factor to consider when making that decision is any pain associated with applying the dressing and frequency of dressing changes. METHODOLOGY: This retrospective study aimed to examine the daily and maximum pain reported by patients and daily opioid consumption to determine if there are any differences among commonly used dressings including 5% sulfamylon solution (SMS), manuka honey, negative-pressure wound therapy (NPWT), silver sulfadiazine, and silver nylon. RESULTS: This study demonstrated that silver sulfadiazine had lower mean daily pain scores compared only to manuka honey as well as lower maximum scores when compared to all other dressings except silver nylon. Furthermore, the choice of dressing did not have an overwhelming effect on the amount of opioids consumed by patients during their hospital stay with manuka honey having less opioid consumption when compared to only 5% SMS and NPWT only. CONCULSION: Further studies are needed with additional validated pain assessment tools and clinically relevant endpoints to fully elucidate the impact of burn dressings and other topical wound care options on pain.