Search Results (128)

In this review, our intention was to shed some light on the history of sublingual and buccal delivery over the past 75 years. By searching the query sublingual and buccal, we noticed four steady growth periods in the number of publications between 1950 and 2025. The early phase of sublingual and buccal drug delivery (1950–1982) saw limited attempts to explore this delivery route. The exploratory growth phase (1983–1993) was marked by the use of nitroglycerin to treat angina, calcium channel blockers to treat hypertension, ACE inhibitors to treat heart conditions, the use of opioids in pain management therapy, and peptide and hormonal therapy. The diversification and discovery phase (1994–2009) was marked by the introduction of small molecules for the treatment of opioid use disorder and analgesia, the use of animal models to enhance the pharmacokinetic understanding of the sublingual and buccal route, the use of penetration enhancers, peptide and hormonal therapy, and few marked FDA drug approvals in this area. The innovation and integration phase (2010–2025) was marked by the use of nanoparticles, multilayered mucoadhesive systems, pediatric formulations (fast-dissolving films and tablets), immunotherapy and vaccine delivery, and a broad spectrum of therapeutic agents, such as steroids, antifungals, cannabinoids, antidepressants, antipsychotics, and narcotics (e.g., buprenorphine and apomorphine), novel formulations of fentanyl and diazepam for pain and seizure control, and the introduction of buccal vitamin D3 sprays. Understanding the history of sublingual and buccal delivery demonstrates a growing area of research focused on enhancing mucosal drug delivery for achieving local and systemic therapeutic benefits. Full article

Background: Postoperative ocular inflammation is a frequent complication of eye surgeries commonly managed using corticosteroids or nonsteroidal anti-inflammatory drug (NSAIDs) eye drops. However, poor ocular bioavailability and patient non-adherence due to frequent dosing limit the therapeutic efficacy of conventional eye drops. This study aimed to develop a sustained-release ocular insert containing bromfenac sodium (BS)-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) with an initial 3% (w/w) free BS fraction incorporated into a poly(vinyl alcohol) (PVA) matrix designed to achieve a dual-phase release profile for improved postoperative therapy. Methods: PLGA-based MPs were fabricated using a double emulsion solvent evaporation technique and incorporated into PVA films to produce ocular inserts with varying MP content. Formulations were characterized for morphology, particle size, zeta potential, drug loading, entrapment efficiency, mucoadhesion, drug distribution, and in vitro release. Data were analyzed by an ANOVA and t-tests with p < 0.05 as significance. Results: MPs were smooth, spherical, and well-dispersed in the PVA inserts. Particle sizes ranged from 3.7 to 5.6 µm, with drug loading 7–8% and entrapment efficiencies 47–52%. Multiphoton imaging confirmed uniform drug distribution. In vitro release showed a dual-phase profile with an initial burst followed by sustained release for up to 4 days, with only negligible further release through Day 6 in one formulation (M1-7525). Conclusions: The developed BS-loaded PLGA MP/PVA insert demonstrated a dual-phase release profile relevant to postoperative ocular inflammation. Its biodegradable, single-application design holds promise for enhancing compliance and therapeutic outcomes in ophthalmic care. Full article

Background: Oral squamous cell carcinoma (OSCC) is one of the most serious forms of cancer in the world. The opportunities to decrease the mortality rate would lie in the possibility of earlier identification of this pathology, and at the same time, the immediate approach of anticancer therapy. Furthermore, new treatment strategies for OSCC are needed to improve existing therapeutic options. Bioactive compounds found in medicinal plants could be used to support these strategies. It is already known that they have an increased potential for action and a safety profile; therefore, they could improve the therapeutic effect of classical chemotherapeutic agents in combination therapies. Methodology: This research was based on an extensive review of recently published studies in scientific databases (PubMed, Scopus, and Web of Science). The selection criteria were based on experimental protocols investigating molecular mechanisms, synergistic actions with conventional anticancer agents, and novel formulation possibilities (e.g., nanoemulsions and mucoadhesive films) for the targeted delivery of bioactive compounds in OSCC. Particular attention was given to in vitro, in vivo, translational, and clinical studies that have proven therapeutic relevance. Results: Recent discoveries regarding the effect of bioactive compounds in the treatment of oral cancer were analyzed, with a view to integrating them into oncological practice for increasing therapeutic efficacy and reducing the occurrence of adverse reactions and treatment resistance. Conclusions: Significant progress has been achieved in this review, allowing us to appreciate that the valorization of these bioactive compounds is emerging. Full article

Antimicrobial resistance in infected chronic wounds present significant risk of complications (e.g., amputations, fatalities). This research aimed to formulate honey-loaded hydrocolloid film comprising gelatin and HPMC, for potential treatment of infected chronic wounds. Honeys from different sources (Cameroonian and Manuka) were used as the bioactive ingredients and their functional characteristics evaluated and compared. The formulated solvent cast films were functionally characterized for tensile, mucoadhesion and moisture handling properties. The morphology and physical characteristics of the films were also analyzed using FTIR, X-ray diffraction and scanning electron microscopy. Antibacterial susceptibility testing was performed to study the inhibition of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus by honey components released from the films. The % elongation values (8.42–40.47%) increased, elastic modulus (30.74–0.62 Nmm) decreased, the stickiness (mucoadhesion) (0.9–1.9 N) increased, equilibrium water content (32.9–72.0%) and water vapor transmission rate (900–298 gm² day⁻¹) generally decreased, while zones of inhibition (2.4–6.5 mm) increased with increasing honey concentration for 1 and 5% w/v, respectively. The results generally showed similar performance for the different honeys and demonstrate the efficacy of honey-loaded hydrocolloid films as potential wound dressing against bacterial growth and potential treatment of infected chronic wounds. Full article

Xerostomia significantly compromises oral comfort, mucosal integrity, and denture retention. While topical therapies such as oral gels are commonly used to manage symptoms, their effectiveness remains limited due to an inability to replicate the complex biochemical and mechanical functions of natural saliva. This review explores the pathophysiology of salivary dysfunction, the structural and functional roles of mucins, and the tribological and rheological demands of the oral environment—particularly in denture wearers. Emphasis is placed on the interplay between mucosal surfaces, salivary films, and prosthetic biomaterials, as well as the importance of mucoadhesion and aqueous boundary lubrication. A rheological comparison of commercially available oral gels and whole human saliva (WHS) reveals that gels are significantly more viscous and elastic, yet fail to mimic the dynamic responsiveness of saliva. Current formulations lack functional standardization and labeling, limiting clinical guidance. The study proposes design principles for next-generation gels that incorporate amphiphilic, biomimetic components and measurable performance benchmarks. Full article

This study aimed to develop and optimize polyvinyl alcohol (PVA)-based polymeric films containing resveratrol (RSV) and to evaluate their applicability as oral mucosal wound dressings. Given the dynamic and complex nature of the oral environment, physicochemical parameters such as elasticity, mucoadhesive strength, and the release profile of the RSV were systematically investigated. The therapeutic performance of pure resveratrol was compared with that of an extract derived from Reynoutria japonica. Films were fabricated using a solvent casting method and characterized in terms of thickness uniformity, weight, color consistency, and flexibility, all of which met the required pharmaceutical criteria. Two tested formulations, FR2 (RSV/PVA/PVP/MCA15C/NaCMC/W/PGE), FE2 (extract/PVA/PVP/MCA15C/NaCMC/W/PGE), showed the best mucoadhesive properties (261.11 ± 0.5 g for FR2 and 299.43 ± 0.38 g for FE2) and a favorable release profile both in water (72.42% for FR2, 77.23% for FE2) and in saliva (49.74% for FR2, 49.70% for FE2). Moreover, the optimized films are characterized by hydrophilicity (contact angle < 90°) and the pH value of the extract after their blurring is close to physiological, which promotes better tolerance and reduces the risk of irritation. Obtained results for polymeric films with resveratrol and R. japonica extract confirmed their great potential for use in dentistry as modern, mucoadhesive dressings, improving the effectiveness of local therapies. Full article

Hydroxypropyl methylcellulose (Hypromellose, HPMC) is a well-known excipient used in the pharmaceutical and nutraceutical fields due to its versatile physicochemical properties. HPMC (derived from cellulose and obtained through etherification) varies in polymerization degree and viscosity, factors that both influence its functional applications. Usually, an increased polymerization degree implies a higher viscosity, depending also on the amount of polymer used. Hypromellose plays a crucial role in solid dosage forms, serving as a binder in the case of controlled-release tablets, a film-forming agent in the case of orodispersible films and mucoadhesive films, and a release modifier due to its presence in different polymerization degrees in the case of extended or modified release tablets. However, its compatibility with other excipients and the active ingredient must be carefully evaluated to prevent formulation challenges via several analytical methods such as differential scanned calorimetry (DSC), Fourier Transformed Infrared spectroscopy (FT-IR), X-Ray Particle Diffraction (XRPD), and Scanning Electron Microscopy (SEM). This review explores the physicochemical characteristics, and diverse applications of HPMC, emphasizing its significance in modern drug delivery systems. Full article

Background: The incorporation of polymers into drug delivery vehicles has been shown to be an effective strategy to prolong the residence time of active ingredients in the precorneal tear film and to increase ocular bioavailability. Objectives: The aim of this study was to develop novel, viscous eye drops containing olopatadine (OCH) as the active ingredient, polysaccharides hydroxypropyl guar gum (HPG), and sodium hyaluronate (SH), individually, and in combination as functional polymers. Methods: Viscous eye drops containing 0.1% OCH in combination with HPG (0.25%) and SH (0.4%), were prepared and evaluated for their physicochemical properties, rheological behavior, mucoadhesion, and preliminary stability. A novel rheological method was used to evaluate the resistance of the eye drops under simulated blinking conditions. In vivo efficacy was evaluated using an ocular itch test in mice to compare the formulations with a commercial product. Results: The formulations remained stable and transparent, with physicochemical parameters within acceptable ranges. Rheological studies confirmed pseudoplastic flow, with the HPG-SH combination exhibiting enhanced viscosity and shear-thinning properties for prolonged retention in the eye. Mucoadhesion was highest in SH-HPG formulations. During simulated blinking cycles, eye drops containing a combination of SH and HPG polymers fully regained their initial viscosity during the resting periods. Preliminary stability studies indicate that the formulated eye drops exhibit satisfactory physicochemical stability under various storage conditions. In vivo, OCH-SH and OCH-HPG-SH drops provided prolonged antipruritic and analgesic effects compared to the reference product. Conclusions: Polysaccharide-based innovative formulations improve OCH retention, enhancing therapeutic efficacy and patient compliance in the treatment of allergic conjunctivitis. Full article

Background: Captopril (CAP), an angiotensin-converting enzyme inhibitor (ACEI), is widely prescribed for managing hypertension, heart failure, and related conditions. When administered orally, CAP undergoes hepatic metabolism, resulting in a bioavailability of 60–75%. However, to bypass the first-pass metabolism and other limitations of the oral route, mucoadhesive buccal films have gained attention as a promising alternative with several advantages. The aim of this work was the formulation and optimization of chitosan-ascorbate mucoadhesive films for buccal delivery of CAP for the management of a hypertension crisis (10 mg and 20 mg) by employing quality by design (QbD) principles and the design of experiment (DoE) approach. Materials and methods: In the present work, chitosan (CHI) was selected as a film-forming agent due to its permeability-enhancing properties, which could be further improved through salification with ascorbic acid (AA). The polymer films were prepared by the solvent casting method. Results: The optimized CAP-loaded formula showed appropriate in vitro mucoadhesion force (>15 N) and breaking hardness (>14 N). The different CAP-containing films had a high drug content (>95%) with homogeneous drug distribution, thus complying with the requirements of Pharmacopeia. FT-IR and RAMAN spectroscopy analyses demonstrated successful incorporation of the drug, and interaction was observed between the excipients of the films, especially in the form of hydrogen bonds. The dissolution test showed immediate release of the API with a similar release pattern from both concentrations of CAP-loaded films. Conclusions: The properties of the prepared films met the predetermined critical quality attribute requirements. The optimized formula of CHI 1.4%, AA 2.5%, and glycerol 0.3% appears to be a promising buccal drug delivery system for CAP. Full article

Hydrogel delivery systems are popular dosage forms that have a number of advantages, such as ease of use, painlessness, increased efficiency due to prolongation of rheological, swelling and sorption characteristics, regulation of drug release, and stimulus sensitivity. Particular interest is shown in hydrogels of cellulose ether derivatives due to the possibility of obtaining their modified forms to vary the solubility, the degree of prolonged action, and the release of the active substance, as well as their widespread availability, affordability, and the possibility of sourcing raw materials from different sources. Hydroxypropyl methylcellulose (HPMC, “hypromellose”) is one of the most popular cellulose ethers in the production of medicines as a filler, coating and carrier. Research on hydrogel carriers based on polymer complexes and modified forms of HPMC using acrylic, citric, and lactic acids, PVP, chitosan, Na-CMC, and gelatin is of particular interest, as they provide the necessary rheological and swelling characteristics. There is growing interest in medical transdermal hydrogels, films, capsules, membranes, nanocrystals, and nanofibers based on HPMC with the incorporation of biologically active substances (BASs), especially those of plant origin, as antibacterial, wound-healing, antimicrobial, mucoadhesive, anti-inflammatory, and antioxidant agents. The aim of this article is to review modern research and achievements in the field of hydrogel systems based on cellulose ethers, particularly HPMC, analyzing their properties, methods of production, and prospects for application in medicine and pharmacy. Full article

Donepezil (DH), a selective acetylcholinesterase inhibitor, is widely used to manage symptoms of mild to moderate Alzheimer’s disease by enhancing cholinergic neurotransmission and preventing acetylcholine breakdown. Despite the effectiveness of oral formulations, extensive hepatic metabolism and low systemic bioavailability have driven the search for alternative delivery systems. This study focuses on nasal delivery as a non-parenteral substitute, utilizing hydroxypropyl methylcellulose (HPMC) for its mucoadhesive properties and methyl-β-cyclodextrin (Me-β-CD) for its ability to enhance permeability and form inclusion complexes with drugs. Prior studies demonstrated the potential of HPMC-based nasal films for nose-to-brain delivery of donepezil and highlighted Me-β-CD’s role in improving drug solubility. Building on this, transparent gel formulations containing DH, HPMC, and 2,6 Me-β-CD were developed to investigate molecular interactions within two- and three-component systems. This study utilized a combination of nuclear magnetic resonance (NMR) spectroscopy and density functional theory (DFT) to provide detailed insights into the interactions between DH, 2,6-Me-β-CD, and HPMC. The findings provide critical insights into drug–excipient interactions, aiding the optimization of stability, solubility, and controlled release. This advances the rational design of nanotechnology-based drug delivery systems for enhanced therapeutic efficacy. Full article

The objective of this work was to investigate the use of nanocrystalline cellulose (NCC) as a drug-delivery excipient for buccal films. Gel-like dispersions were created by blending either gel or powder NCC (gNCC or pNCC) with natural polymers (alginate, pectin, or chitosan) in water, with glycerol serving as a plasticiser. Ibuprofen (IBU) as an active pharmaceutical ingredient (API) was dissolved in a self-microemulsifying drug delivery system (SMEDDS) to improve its solubility prior to its addition to gel-like dispersions. Dispersions were dried, and resulting films were cut to 3 cm × 1.5 cm size, appropriate for buccal delivery. Rheological measurements revealed that shorter, thinner, and less crystalline nanocellulose fibres are more favourable for stronger gel properties. While overall, weaker gel structure prior to film casting also resulted in shorter disintegration time, this was not the case for NCC–chitosan films; here, the low solubility of chitosan in neutral media proved to be the main obstacle. Nevertheless, the prolonged disintegration of NCC–chitosan films did not impact the dissolution of IBU, as these films exhibited the fastest dissolution rate, followed by NCC–pectin and NCC–alginate. Furthermore, NCC properties significantly influenced the dissolution behaviour of the chitosan formulations, with gNCC favouring faster IBU release due to weaker gel formation prior to film casting. Full article

Background/Objectives: The oral delivery of large-molecule drugs remains challenging due to poor solubility, perdemeability, and stability in the gastrointestinal tract, resulting in low bioavailability. In this study, hot melt extrusion (HME) was investigated as a solvent-free manufacturing technique for mucoadhesive bilayer films to improve drug absorption. Methods: Polyvinyl alcohol (PVA) and polyethylene oxide (PEO) were evaluated as mucoadhesive film-forming polymers, in conjunction with Eudragit^® RS as a water-insoluble backing layer. Paracetamol and lactase were utilized as small and large molecule APIs, respectively. The resulting films were assembled into bilayer film samples and examined for mechanical properties, mucoadhesion, and dissolution behavior. A novel dissolution model was developed to evaluate unidirectional drug transport. Results: The results showed that bilayer films could be successfully fabricated using HME, with different mechanical properties depending on the polymer and drug content. Tests with the newly developed dissolution model showed a unidirectional drug release. The model also confirmed the need for biorelevant dissolution test systems because of a better differentiation between polymers compared to standard test methods such as the paddle-over-disk method. Furthermore, the investigation revealed that the activity of enzymes was retained after extrusion, thus indicating the feasibility of processing biologics. Conclusions: This study highlights the potential of HME to produce bilayer films as an innovative drug delivery platform offering improved bioavailability for both small and large molecules. Full article

This research aimed to develop mucoadhesive buccal films incorporating nanostructured lipid carriers (NLCs) loaded with triamcinolone acetonide (TN-films). A Box–Behnken design was employed as a systematic approach to optimize the formulation. Key components of the NLCs—spermaceti, soybean oil, and polysorbate 80—were considered independent variables. The NLCs were prepared and size-reduced using a combination of hot homogenization and ultrasonic probe techniques. Films were cast using hydroxypropyl methylcellulose (HPMC) as the film-forming agent. The TN-films were characterized based on weight, thickness, tensile strength, elongation at break, contact angle, and surface free energy. Linear regression showed that spermaceti increased film weight and thickness, while polysorbate 80 decreased them. The mechanical strength of the films was primarily influenced by spermaceti; higher concentrations of spermaceti resulted in decreased film strength. Additionally, all independent variables contributed positively to the lipophilicity of the films. The TN-films were found to sustain drug release via a Fickian diffusion mechanism, exhibiting rapid swelling and favorable mucoadhesive properties. Moreover, the TN-films demonstrated superior drug release and permeation to pastes and films loaded with emulsions. These findings suggest that the TN-films represent a promising and effective approach for the buccal delivery of triamcinolone acetonide. Full article

Chitosan is a positively charged natural polymer with several properties conducive to wound-healing applications, such as biodegradability, structural integrity, hydrophilicity, adhesiveness to tissue, and bacteriostatic potential. Along with other mechanical properties, some of the properties discussed in this review are antibacterial properties, mucoadhesive properties, biocompatibility, high fluid absorption capacity, and anti-inflammatory response. Chitosan forms stable complexes with oppositely charged polymers, arising from electrostatic interactions between (+) amino groups of chitosan and (−) groups of other polymers. These polyelectrolyte complexes (PECs) can be manufactured using various materials and methods, which brings a diversity of formulations and properties that can be optimized for specific wound healing as well as other applications. For example, chitosan-based PEC can be made into dressings/films, hydrogels, and membranes. There are various pros and cons associated with manufacturing the dressings; for instance, a layer-by-layer casting technique can optimize the nanoparticle release and affect the mechanical strength due to the formation of a heterostructure. Furthermore, chitosan’s molecular weight and degree of deacetylation, as well as the nature of the negatively charged biomaterial with which it is cross-linked, are major factors that govern the mechanical properties and biodegradation kinetics of the PEC dressing. The use of chitosan in wound care products is forecasted to drive the growth of the global chitosan market, which is expected to increase by approximately 14.3% within the next decade. This growth is driven by products such as chitoderm-containing ointments, which provide scaffolding for skin cell regeneration. Despite significant advancements, there remains a critical gap in translating chitosan-based biomaterials from research to clinical applications. Full article