Search Results (6)

Background/Objectives: Topical treatment of cutaneous tuberculosis (CTB) requires reliable models to evaluate dermal drug release and diffusion, particularly for fixed-dose combinations (FDCs) with contrasting physicochemical properties. Human skin remains the reference standard but poses ethical, logistical, and reproducibility challenges. This study investigated the suitability of Strat-M^® synthetic membranes as an alternative to human skin for assessing the simultaneous release and diffusion of clofazimine (CFZ) and pyrazinamide (PZA) from a topical FDC, and aimed to develop an optimized dermal emulsion using a Quality-by-Design (QbD)-informed formulation development tool. Methods: Self-emulsifying dermal emulsions containing CFZ and PZA were developed following QbD principles. Preformulation studies included drug solubility screening, oil phase selection, and pseudoternary phase diagram construction to identify stable emulsion regions. Formulations were characterized for droplet size, polydispersity index, zeta potential, viscosity, self-emulsification efficiency, and thermodynamic stability. Eight stable emulsions were identified, of which four were selected for in vitro drug release studies. The peppermint oil-based emulsion (PPO415) was further evaluated in comparative diffusion studies using Strat-M^® membranes and ex vivo human skin (Caucasian and African). Results: PPO415 demonstrated favorable physicochemical properties, including high CFZ solubility, uniform droplet distribution, and suitability for dermal application. Comparative diffusion studies showed that Strat-M^® underestimated the partitioning of lipophilic CFZ while overestimating the diffusion of hydrophilic PZA relative to human skin. These differences were attributed to compositional and structural disparities between synthetic membranes and biological skin. Conclusions: Strat-M^® membranes show potential as a reproducible and ethical in vitro screening tool during early-stage formulation development for topical FDCs. However, ex vivo human skin remains essential for accurately predicting dermal drug distribution and therapeutic performance. Full article

Background/Objectives: Cutaneous tuberculosis (CTB) represents a rare extrapulmonary manifestation of Mycobacterium tuberculosis infection, accounting for approximately 1–2% of all tuberculosis cases. Despite its low incidence, CTB remains diagnostically challenging due to its clinical polymorphism and resemblance to other granulomatous or neoplastic dermatoses. Among its variants, lupus vulgaris (LV) constitutes the most common and indolent form in regions of moderate tuberculosis endemicity. The present study aims to highlight the diagnostic complexity, management, and long-term outcomes of LV, emphasizing its potential for malignant transformation into squamous cell carcinoma (SCC). Methods: We present a detailed case of lupus vulgaris in a male patient with a prolonged disease course, refractory to initial empiric therapy, successfully managed through anti-tubercular therapy (ATT) followed by surgical excision. A review of the literature was conducted to contextualize this case within the broader clinical spectrum of CTB, with particular attention to epidemiology, histopathology, and complications, including SCC development. Results: The patient demonstrated significant clinical improvement following standard six-month ATT; however, residual fibrotic lesions required excision for definitive management. Literature review revealed that chronic LV lesions persisting for decades may undergo malignant transformation. Analysis of reported cases underscores the importance of vigilance and early surgical intervention in long-standing or atypical LV. Conclusions: Lupus vulgaris remains a clinically deceptive entity requiring multidisciplinary management. Early recognition, appropriate ATT, and surgical excision of residual or recalcitrant lesions are crucial to prevent complications, including carcinogenesis. Greater clinician awareness of CTB’s diverse presentations may reduce diagnostic delays and improve outcomes. Full article

Background: Tuberculosis remains a significant global health issue, and the rise of drug-resistant strains is becoming increasingly concerning. Currently, treatment options are limited to systemic regimens; however, developing topical drug delivery systems could offer advantages for treating cutaneous tuberculosis (CTB) when applied directly to the lesions. We developed topical emulsions using the self-emulsification mechanism that combine fixed doses of isoniazid (INH) and rifampicin (RIF) using a quality-by-design approach. Methods: Preformulation studies pertaining to drug solubility in various solvents, the construction of pseudoternary diagrams to identify self-emulsification regions for each tested excipient combination, and the preparation of checkpoint formulations were conducted and visually examined. Formulations displaying no physical instabilities were subsequently exposed to characterization experiments, including droplet size determination, zeta potential, size distribution, viscosity, pH, self-emulsification, cloud point, robustness to dilution, and thermodynamic stability assessment. Three selected formulations were consequently subjected to membrane release experiments, followed by skin diffusion studies, and INH and RIF stability in these emulsions was determined, because these drugs have a known interaction. Conclusions: While incorporating essential oils in a topical formulation improved RIF solubility, it also resulted in several instabilities. RIF exhibited greater susceptibility to degradation under higher temperatures and lower pH conditions. However, drug release from all formulations tested was confirmed. Notably, olive oil microemulsions demonstrated the most favorable characteristics for dermal drug delivery; nonetheless, drug diffusion into and through the skin (which was not desired) could not be quantified. Despite these challenges, the findings indicate that topical drug delivery systems using the self-emulsification process can facilitate the direct treatment of CTB. Full article

Tuberculosis is an ancient disease that humanity struggled with for centuries and continues to struggle with. The bacteria Mycobacterium tuberculosis often infects the lungs through respiratory transmission and manifests itself through various symptoms, including cutaneous infections. Cutaneous tuberculosis (CTB) comprises about 1% to 1.5% of all extrapulmonary manifestations and is often accompanied by polymorphous lesions, including papules, nodules, plaques, ulcers, gummas, and verrucous lesions. CTB is most commonly observed in low-income, HIV, and immunosuppressed populations, similar to intrapulmonary manifestations. The main pathogen for CTB is M. tuberculosis but less commonly with M. bovis and BCG vaccine, and the modes of transmission are largely classified into exogenous and endogenous CTB. Current treatment options for CTB include oral therapy of antibiotic medications such as rifampicin, streptomycin, ethambutol, isoniazid, and pyrazinamide, which is occasionally combined with surgical intervention. Full article

Cutaneous tuberculosis (CTB) is a very rare disease and accounts for only 1–2% of cases of extrapulmonary tuberculosis (EPTB). Due to the variety of its clinical manifestations, the uncharacteristic appearance of its lesions, resembling other dermatoses in the early stages, and the limited experience of clinicians due to the rarity of CTB, diagnosis is very difficult. Particularly noteworthy is the fact that most cases of EPTB, including skin tuberculosis (TB), can be a manifestation of systemic involvement. In this paper, we present a case of an immunocompromised patient who was diagnosed with CTB almost a year after the first dermatological lesions were located on the lower extremities. At the same time, due to respiratory symptoms, a diagnosis of pulmonary TB (PTB) was made, and radiological and microbiological confirmations were obtained. Full article

Although chemotherapeutic treatment regimens are currently available, and considerable effort has been lavished on the development of new drugs for the treatment of tuberculosis (TB), the disease remains deeply intractable and widespread. This is due not only to the nature of the life cycle and extraordinarily disseminated habitat of the causative pathogen, principally Mycobacterium tuberculosis (Mtb), in humans and the multi-drug resistance of Mtb to current drugs, but especially also to the difficulty of enabling universal treatment of individuals, immunocompromised or otherwise, in widely differing socio-economic environments. For the purpose of globally eliminating TB by 2035, the World Health Organization (WHO) introduced the “End-TB” initiative by employing interventions focusing on high impact, integrated and patient-centered approaches, such as individualized therapy. However, the extraordinary shortfall in stipulated aims, for example in actual treatment and in TB preventative treatments during the period 2018–2022, latterly and greatly exacerbated by the COVID-19 pandemic, means that even greater pressure is now placed on enhancing our scientific understanding of the disease, repurposing or repositioning old drugs and developing new drugs as well as evolving innovative treatment methods. In the specific context of multidrug resistant Mtb, it is furthermore noted that the incidence of extra-pulmonary TB (EPTB) has significantly increased. This review focusses on the potential of utilizing self-double-emulsifying drug delivery systems (SDEDDSs) as topical drug delivery systems for the dermal route of administration to aid in treatment of cutaneous TB (CTB) and other mycobacterial infections as a prelude to evaluating related systems for more effective treatment of CTB and other mycobacterial infections at large. As a starting point, we consider here the possibility of adapting the highly lipophilic riminophenazine clofazimine, with its potential for treatment of multi-drug resistant TB, for this purpose. Additionally, recently reported synergism achieved by adding clofazimine to first-line TB regimens signifies the need to consider clofazimine. Thus, the biological effects and pharmacology of clofazimine are reviewed. The potential of plant-based oils acting as emulsifiers, skin penetration enhancers as well as these materials behaving as anti-microbial components for transporting the incorporated drug are also discussed. Full article