Characterization of Prototype Gummy Formulations Provides Insight into Setting Quality Standards.

Gummy formulations are considered suitable alternatives to traditional oral dosage forms like tablets and capsules due to their merits that include chewability, softness/flexibility, improved drug release, administration without water, appealing organoleptic properties, better patient compliance, easy preparation and usefulness for persons of different ages (e.g. children). Though there is increasing interest in gummy formulations containing drugs, measurable parameters, and specification limits for evaluating their quality are scarce. Quality check forms an essential part of the pharmaceutical development process because drug products must be distributed as consistently stable, safe, and therapeutically effective entities. Consequently, some quality parameters that could contribute to the overall performance of typical gummy formulations were investigated employing six brands of non-medicinal gummies as specimens. Accordingly, key physicochemical and micromechanical characteristics namely adhesiveness (0.009 - 0.028 mJ), adhesive force (0.009 - 0.055 N), chewiness (2.780 - 6.753 N), cohesiveness (0.910 - 0.990), hardness (2.984 - 7.453 N), springiness (0.960 - 1.000), and resilience (0.388 - 0.572), matrix firmness - compression load (2.653 - 6.753 N) and work done (3.288 - 6.829 mJ), rupture (5.315 - 29.016 N), moisture content (< 5%), weight uniformity (< 2.5 g; < 7.5% deviation), and intraoral dissolution pH (≥ 3.5 ≤ 6.8) were quantified to identify measures that may potentially function as specification limits and serve as prospective reference points for evaluating the quality of gummy formulations. Findings from this work contribute to ongoing efforts to standardize the quality control strategies for gummy formulations, particularly those intended for oral drug delivery.

Leading Paediatric Infectious Diseases-Current Trends, Gaps, and Future Prospects in Oral Pharmacotherapeutic Interventions.

Paediatric infectious diseases contribute significantly to global health challenges. Conventional therapeutic interventions are not always suitable for children, as they are regularly accompanied with long-standing disadvantages that negatively impact efficacy, thus necessitating the need for effective and child-friendly pharmacotherapeutic interventions. Recent advancements in drug delivery technologies, particularly oral formulations, have shown tremendous progress in enhancing the effectiveness of paediatric medicines. Generally, these delivery methods target, and address challenges associated with palatability, dosing accuracy, stability, bioavailability, patient compliance, and caregiver convenience, which are important factors that can influence successful treatment outcomes in children. Some of the emerging trends include moving away from creating liquid delivery systems to developing oral solid formulations, with the most explored being orodispersible tablets, multiparticulate dosage forms using film-coating technologies, and chewable drug products. Other ongoing innovations include gastro-retentive, 3D-printed, nipple-shield, milk-based, and nanoparticulate (e.g., lipid-, polymeric-based templates) drug delivery systems, possessing the potential to improve therapeutic effectiveness, age appropriateness, pharmacokinetics, and safety profiles as they relate to the paediatric population. This manuscript therefore highlights the evolving landscape of oral pharmacotherapeutic interventions for leading paediatric infectious diseases, crediting the role of innovative drug delivery technologies. By focusing on the current trends, pointing out gaps, and identifying future possibilities, this review aims to contribute towards ongoing efforts directed at improving paediatric health outcomes associated with the management of these infectious ailments through accessible and efficacious drug treatments.

State of the art in pediatric nanomedicines.

In recent years, the continuous development of innovative nanopharmaceuticals is expanding their biomedical and clinical applications. Nanomedicines are being revolutionized to circumvent the limitations of unbound therapeutic agents as well as overcome barriers posed by biological interfaces at the cellular, organ, system, and microenvironment levels. In many ways, the use of nanoconfigured delivery systems has eased challenges associated with patient differences, and in our opinion, this forms the foundation for their potential usefulness in developing innovative medicines and diagnostics for special patient populations. Here, we present a comprehensive review of nanomedicines specifically designed and evaluated for disease management in the pediatric population. Typically, the pediatric population has distinguishing needs relative to those of adults majorly because of their constantly growing bodies and age-related physiological changes, which often need specialized drug formulation interventions to provide desirable therapeutic effects and outcomes. Besides, child-centric drug carriers have unique delivery routes, dosing flexibility, organoleptic properties (e.g., taste, flavor), and caregiver requirements that are often not met by traditional formulations and can impact adherence to therapy. Engineering pediatric medicines as nanoconfigured structures can potentially resolve these limitations stemming from traditional drug carriers because of their unique capabilities. Consequently, researchers from different specialties relentlessly and creatively investigate the usefulness of nanomedicines for pediatric disease management as extensively captured in this compilation. Some examples of nanomedicines covered include nanoparticles, liposomes, and nanomicelles for cancer; solid lipid and lipid-based nanostructured carriers for hypertension; self-nanoemulsifying lipid-based systems and niosomes for infections; and nanocapsules for asthma pharmacotherapy.

A child-friendly anti-infective gummy formulation: Design, physicochemical, micromechanical, and taste sensory evaluation.

The shortage of child friendly formulations constitutes a key part of the major challenges impeding the successful management of tuberculosis disease in the paediatric population. Chewable formulations are an attractive alternative to traditional preparations like tablets and suspensions owing to the possibility for taste masking, administration without water, their unique physical appeal, visually appeasing shapes, and useability in children 2 years old and above. Consequently, we designed a polymeric gummy drug formulation (P-GDF), herein referred to as the FlexiChew formulation, containing a first-line antitubercular agent, isoniazid, using a combined solid-liquid dispersion and temperature dependent sol-gel processing technique. The resulting P-GDF was visually attractive, supple, easy to handle, dimensionally compact (17.738 ± 0.779 mm height, 10.473 ± 0.944 mm width, and 8.603 ± 0.852 mm thickness), light weight (1.425 ± 0.038 g), mechanically robust (hardness = 37.260 ± 4.66 N; resilience = 0.542 ± 0.029), and potentially easy to masticate (chewiness = 30.570 ± 13.090 N; cohesiveness = 0.800 ± 0.283%; adhesiveness = 0.018 ± 0.007 mJ). It was structurally intact, effectively encapsulated isoniazid (101.565 ± 4.181%), and released it (≈100% in 75 min) following zero order and non-Fickian mechanisms in different dissolution media. Besides, it displayed efficient taste masking and palatability relative to its placebo (signal distance = 54). Short-term stability studies revealed optimal storage conditions to be under controlled ambient environments, away from direct light, and without desiccants. Thus, a child friendly isoniazid-loaded edible gummy drug formulation was successfully fabricated with the goal of improving adherence and therapeutic efficacy.

Nanofibrous Scaffolds for Diabetic Wound Healing.

Chronic wounds are one of the secondary health complications that develop in individuals who have poorly managed diabetes mellitus. This is often associated with delays in the wound healing process, resulting from long-term uncontrolled blood glucose levels. As such, an appropriate therapeutic approach would be maintaining blood glucose concentration within normal ranges, but this can be quite challenging to achieve. Consequently, diabetic ulcers usually require special medical care to prevent complications such as sepsis, amputation, and deformities, which often develop in these patients. Although several conventional wound dressings, such as hydrogels, gauze, films, and foams, are employed in the treatment of such chronic wounds, nanofibrous scaffolds have gained the attention of researchers because of their flexibility, ability to load a variety of bioactive compounds as single entities or combinations, and large surface area to volume ratio, which provides a biomimetic environment for cell proliferation relative to conventional dressings. Here, we present the current trends on the versatility of nanofibrous scaffolds as novel platforms for the incorporation of bioactive agents suitable for the enhancement of diabetic wound healing.

Orally disintegrating drug carriers for paediatric pharmacotherapy.

Non-compliance, dosing inaccuracy, choking risk, flavour, and instability, are some of the issues associated with paediatric, oral dosage forms - tablets, capsules, solutions, and suspensions. Orally disintegrating drug carriers, a dosage form with growing interest, are thought to overcome several of the challenges associated with these conventional formulations by rapidly disintegrating within the buccal cavity without the need for water. This review serves as an up-to-date report on the various types of orodispersible delivery systems, currently being developed or commercialized, by detailing their characteristics, manufacturing processes, and applications in the paediatric population. Mentioned are orodispersible tablets, films, wafers and lyophilisates, mini-tablets, capsules, granules, electrospun fibers and webs. Also highlighted are the choice of excipients, quality control requirements, and expected pharmacokinetics of orally disintegrating drug carriers concerning the paediatric population. Overall, orodispersible formulations, particularly tablets, films, and lyophilisates/wafers, have shown to be a valuable addition to medication administration in minors, thus the execution of more targeted research and development activities is expected to lead to enhanced paediatric care and outcomes.

Pediatric Tuberculosis Management: A Global Challenge or Breakthrough?

Managing pediatric tuberculosis (TB) remains a public health problem requiring urgent and long-lasting solutions as TB is one of the top ten causes of ill health and death in children as well as adolescents universally. Minors are particularly susceptible to this severe illness that can be fatal post-infection or even serve as reservoirs for future disease outbreaks. However, pediatric TB is the least prioritized in most health programs and optimal infection/disease control has been quite neglected for this specialized patient category, as most scientific and clinical research efforts focus on developing novel management strategies for adults. Moreover, the ongoing coronavirus pandemic has meaningfully hindered the gains and progress achieved with TB prophylaxis, therapy, diagnosis, and global eradication goals for all affected persons of varying age bands. Thus, the opening of novel research activities and opportunities that can provide more insight and create new knowledge specifically geared towards managing TB disease in this specialized group will significantly improve their well-being and longevity.

A Micro-Configured Multiparticulate Reconstitutable Suspension Powder of Fixed Dose Rifampicin and Pyrazinamide: Optimal Fabrication and In Vitro Quality Evaluation.

The scarcity of age-appropriate pharmaceutical formulations is one of the major challenges impeding successful management of tuberculosis (TB) prevalence in minors. To this end, we designed and assessed the quality of a multiparticulate reconstitutable suspension powder containing fixed dose rifampicin and pyrazinamide (150 mg/300 mg per 5 mL) which was prepared employing solid−liquid direct dispersion coupled with timed dehydration, and mechanical pulverization. The optimized formulation had a high production yield (96.000 ± 3.270%), displayed noteworthy powder flow quality (9.670 ± 1.150°), upon reconstitution the suspension flow property was non-Newtonian and was easily redispersible with gentle manual agitation (1.720 ± 0.011 strokes/second). Effective drug loading was attained for both pyrazinamide (97.230 ± 2.570%w/w) and rifampicin (97.610 ± 0.020%w/w) and drug release followed a zero-order kinetic model (R2 = 0.990) for both drugs. Microscopic examinations confirmed drug encapsulation efficiency and showed that the particulates were micro-dimensional in nature (n < 700.000 µm). The formulation was physicochemically stable with no chemically irreversible drug-excipient interactions based on the results of characterization experiments performed. Findings from organoleptic evaluations generated an overall rating of 4.000 ± 0.000 for its attractive appearance and colour 5.000 ± 0.000 confirming its excellent taste and extremely pleasant smell. Preliminary cytotoxicity studies showed a cell viability above 70.000% which indicates that the FDC formulation was biocompatible. The optimized formulation was environmentally stable either as a dry powder or reconstituted suspension. Accordingly, a stable and palatable FDC antimycobacterial reconstitutable oral suspension powder, intended for flexible dosing in children and adolescents, was optimally fabricated.

A Long-Acting Thermoresponsive Injectable Formulation of Tin Protoporphyrin Sustains Antitubercular Efficacy in a Murine Infection Model.

Tuberculosis is the leading cause of death from a single infectious agent, ranking above the human immunodeficiency virus (HIV). Effective treatment using antibiotics is achievable, but poor patient compliance constitutes a major challenge impeding successful pharmacotherapeutic outcomes. This is often due to the prolonged treatment periods required and contributes significantly to the rising incidence of drug resistance, which is a major cause of tuberculosis mortality. Thus, innovative interventions capable of encouraging compliance and decreasing lengthy and frequent dosing are needed. Previously, aqueous tin protoporphyrin IX (SnPPIX), a heme oxygenase-1 inhibitor, administered as multiple daily intraperitoneal (IP) injections, showed considerable antitubercular efficacy and treatment shortening capabilities as a host-directed therapy in infected mice. Since daily IP injection is a clinically impractical administration approach, this proof-of-concept study aims to develop a novel, sustained action injectable formulation of SnPPIX for safe intramuscular (IM) administration. Herein, a SnPPIX-loaded poloxamer-poly(acrylic acid)-based thermoresponsive injectable formulation (SnPPIX-TIF) is designed for effective IM delivery. Results show SnPPIX-TIF is microparticulate, syringeable, injectable, and exhibits complete in vitro/in vivo gelation. Administered once weekly, SnPPIX-TIF significantly prolonged absorption and antimicrobial efficacy in infected mice. In addition, SnPPIX-TIF is well-tolerated in vivo; results from treated animals show no significant histopathologic alterations and were indistinguishable from the untreated control group, thus supporting its biocompatibility and preclinical safety. Overall, the IM delivery of the thermoresponsive injectable formulation safely sustains antitubercular effect in an infected murine model and decreases the number of injections required, signifying a potentially practical approach for future clinical translation.

Optimal Design, Characterization and Preliminary Safety Evaluation of an Edible Orodispersible Formulation for Pediatric Tuberculosis Pharmacotherapy.

The severity of tuberculosis (TB) in children is considered a global crisis compounded by the scarcity of pharmaceutical formulations suitable for pediatric use. The purpose of this study was to optimally develop and evaluate a pyrazinamide containing edible orodispersible film formulation potentially suitable for use in pediatrics actively infected with TB. The formulation was prepared employing aqueous-particulate blending and solvent casting methods facilitated by a high performance Box Behnken experimental design template. The optimized orodispersible formulation was mechanically robust, flexible, easy to handle, exhibited rapid disintegration with initial matrix collapse occurring under 60 s (0.58 ± 0.05 min ≡ 34.98 ± 3.00 s) and pyrazinamide release was controlled by anomalous diffusion coupled with matrix disintegration and erosion mechanisms. It was microporous in nature, light weight (57.5 ± 0.5 mg) with an average diameter of 10.5 mm and uniformly distributed pyrazinamide load of 101.13 ± 2.03 %w/w. The formulation was physicochemically stable with no evidence of destructive drug-excipient interactions founded on outcomes of characterization and environmental stability investigations. Preliminary inquiries revealed that the orodispersible formulation was cytobiocompatible, palatable and remained intact under specific storage conditions. Summarily, an edible pyrazinamide containing orodispersible film formulation was optimally designed to potentially improve TB pharmacotherapy in children, particularly the under 5 year olds.

Development and Evaluation of a Reconstitutable Dry Suspension Containing Isoniazid for Flexible Pediatric Dosing.

Tuberculosis (TB) is a major cause of childhood death. Despite the startling statistics, it is neglected globally as evidenced by treatment and clinical care schemes, mostly extrapolated from studies in adults. The objective of this study was to formulate and evaluate a reconstitutable dry suspension (RDS) containing isoniazid, a first-line anti-tubercular agent used in the treatment and prevention of TB infection in both children and adults. The RDS formulation was prepared by direct dispersion emulsification of an aqueous-lipid particulate interphase coupled with lyophilization and dry milling. The RDS appeared as a cream-white free-flowing powder with a semi-crystalline and microparticulate nature. Isoniazid release was characterized with an initial burst up to 5 minutes followed by a cumulative release of 67.88% ± 1.88% (pH 1.2), 60.18% ± 3.33% (pH 6.8), and 49.36% ± 2.83% (pH 7.4) over 2 hours. An extended release at pH 7.4 and 100% drug liberation was achieved within 300 minutes. The generated release profile best fitted the zero order kinetics (R2 = 0.976). RDS was re-dispersible and remained stable in the dried and reconstituted states over 4 months and 11 days, respectively, under common storage conditions.

Premium ethylcellulose polymer based architectures at work in drug delivery.

Premium ethylcellulose polymers are hydrophobic cellulose ether based biomaterials widely employed as biocompatible templates for the design of novel drug delivery systems. They are classified as United States Food and Drug Administration Generally-Recognized-As-Safe chemical substances and have been extensively utilized within the biomedical and pharmaceutical industries for over half a century. They have so far demonstrated the potential to modulate and improve the physiological performance of bioactives leading to the desired enhanced prophylactic and therapeutic outcomes. This review therefore presents a scholarly survey of inter-disciplinary developments focused on the functionalities of ethylcellulose polymers as biomaterials useful for the design of smart delivery architectures for relevant pharmacotherapeutic biomedical applications. Emphasis was placed on evaluating scientific resources related to recent advancements and future directions associated with its applications as delivery systems for drugs and biologics within the past decade thus complementing other specialized reviews showcasing the theme.

Isoniazid-loaded orodispersible strips: Methodical design, optimization and in vitro-in silico characterization.

Drug treatment remains the most effective global approach to managing and preventing tuberculosis. This work focuses on formulating and evaluating an optimized polyvinyl alcohol-polyethylene glycol based orodispersible strip containing isoniazid, a first-line anti-tubercular agent. A solvent casting method guided through a Taguchi experimental design was employed in the fabrication, optimization and characterization of the orodispersible strip. The optimized strip was physically amalgamated with a monolayer, uniformly distributed surface geometry. It was 159.2 ±â€¯3.0 µm thick, weighed 36.9 ±â€¯0.3 mg, had an isoniazid load of 99.5 ±â€¯0.8%w/w, disintegration and dissolution times of 17.6 ±â€¯0.9 s and 5.5 ±â€¯0.1 min respectively. In vitro crystallinity, thermal measurements and in silico thermodynamic predictions confirmed the strip's intrinsic miscibility, thermodynamic stability and amorphous nature. A Korsmeyer-Peppas (r = 0.99; n > 1 = 1.07) fitted kinetics typified by an initial burst release of 49.4 ±â€¯1.9% at 4 min and a total of 99.8 ±â€¯3.3% at 30 min was noted. Ex vivo isoniazid permeation through porcine buccal mucosa was bi-phasic and characterized by a 50.4 ±â€¯3.8% surge and 95.6 ±â€¯2.9% at 5 and 120 min respectively. The strip was physicomechanically robust, environmentally stable and non-cytotoxic.

Combined Atomistic Molecular Calculations and Experimental Investigations for the Architecture, Screening, Optimization, and Characterization of Pyrazinamide Containing Oral Film Formulations for Tuberculosis Management.

To date, effective treatment, prophylaxis, and control of tuberculosis (TB) infection is mainly dependent on the use of drugs. However, patient noncompliance with prescribed anti-TB treatment schemes remains a major problem confronting successful pharmacotherapeutic outcomes. Thus, the development of alternative delivery systems that can improve adherence for the existing anti-TB bioactives has been intensified in recent times. The aim of this investigation was to engineer an optimal, thermodynamically stable oral film (OF) formulation containing a key anti-TB agent, pyrazinamide (PYZ), employing molecular modeling and experimental tools. Four PYZ-loaded film variants (OF 1, OF 2, OF 3, OF 4) were constructed in silico and then prepared in vitro using the Accelrys Materials Studio software and solvent casting method, respectively. Screening and selection of the optimal OF was based on the computation of the total interaction energy (ET), kinetic energy (EK), solubility parameter (S), and cohesive energy density (CED) as well as determining mass, thickness, dissolution and disintegration times, dissolution pH, drug loading capacity, and surface morphology in vitro. OF 2 was selected as the optimal formulation as it displayed the lowest ET (-8006.28 kcal/mol), dissolution time (9.96 min), disintegration time (56.49 s), and weight (39.33 mg); moderate EK (1052.98 kcal/mol); highest S (44.55 (J/cm(3))(0.5)) and CED (1.99 × 10(9) J/m(3)), slim dimension (166 µm), good and unvarying drug loading capacity (98.04%), acceptable dissolution pH (6.70), and well-layered surface topography. The drug release behavior of the optimal OF 2 was best elucidated with the zero order (R(2) = 0.97) and Korsmeyer-Peppas (R(2) = 0.99) models. X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC) analyses showed that OF 2 was made of physically mixed multiple component polymeric and nonpolymeric compounds. OF 2 was semicrystalline in nature and displayed a dual phased ex vivo mucosal permeation pattern. In silico and in vitro physicomechanical quantities revealed OF 2's flexibility, robustness, and compressibility. OF 2 was most stable under controlled environmental humidity, pressure, and temperature conditions in silico and in vitro. OF 2 was potentially non-cytotoxic and biocompatible. Succinctly, this work demonstrated the applicability of a combination of atomistic molecular mechanics and dynamics calculations as well as experimental analyses to the fabrication, screening, optimization, and characterization of drug formulations. Lastly, the fabricated OF 2 formulation can function as a potential alternative for the effective loading and delivery of PYZ.

In vitro, ex vivo and in silico mechanistic elucidation of the performance of an optimized porosity-controlled multi-elemental transbuccal system.

PURPOSE: To elucidate the mechanisms of construction and performance of a porosity controlled, multi-elemental transbuccal system employing experimental and computational approaches. METHODS: The production of the formulation was guided through a Box-Benkhen design employing homogenization coupled with lyophilization. The physicochemical and physicomechanical properties of the experimental design formulations were quantified with relevant analytical techniques. The influence of changes in porosity measures on the magnitude of these physical properties were explored mathematically. Furthermore, experimental outputs from the Box-Behnken design formulations were fitted into set limits and optimized using the response surface method. The optimized porosity-controlled formulation was subjected to mechanistic experimental and computational elucidations. RESULTS: In general, the changes in magnitudes of studied porosity quantities had significant impact on formulation physicochemical and physicomechanical properties. The generation of an optimized formulation validated the stability and accuracy of the Box-Behnken experimental design. Experimental investigations revealed that the construction of this formulation is as a result of non-destructive physical interactions amongst its make-up compounds while its mechanism of performance is anchored mainly upon a gradual collapse of its ordered porous structure. Furthermore, the molecule mechanics simulations quantitatively predicted the molecular interactions inherent to multicomponent matrix formation and the mucoadhesion mechanism. CONCLUSIONS: The fabrication and performance mechanisms of the porosity-controlled transbuccal system was successfully explored.

In vivo and ex vivo evaluation of a multi-particulate composite construct for sustained transbuccal delivery of carbamazepine.

Carbamazepine (CBZ) is a leading molecule in the management of epilepsy. Surveys have revealed that a sufficient lack of therapeutically efficient CBZ transbuccal formulation exists. Therefore, this investigation was directed toward designing multiparticulate composite construct (MCC) for the transbuccal delivery of CBZ. The MCC was formulated using interphase, coparticulate­cosolvent homogenization technique, and lyophilization. In vitro, ex vivo, and in vivo investigations were performed. The mesoporous (pore width = 80.1233 Å) MCC was mechanically stable (Є(D) = 0.0290 J, M(F) = 8.5490 N/mm) and resilient (M(R) = 5.5040%). It demonstrated distinctive controlled release (9.9800%/h), permeation enhancing (10.8730%/h), drug loading (90.0541%), and bioadhesive (ω(adh) = 0.0034 J, F(det) = 1.0751 N) capacities. In vivo studies on pigs showed the ability of the MCC to effectively initiate and regulate transbuccal permeation of CBZ as visualized by outcomes of the quantitative and qualitative assessments of isolated plasma samples. Furthermore, comparisons of in vitro and in vivo data of MCC with a conventional product highlighted its capability to attain higher bioavailability and more controlled release trends. Histological and cytological investigations confirmed that the MCC is biocompatible. The mathematical model produced relevant pharmacokinetics and in vitro/in vivo correlation information.

Evaluation of the impacts of formulation variables and excipients on the drug release dynamics of a polyamide 6,10-based monolithic matrix using mathematical tools.

Drug release from hydrophilic matrices is regulated mainly by polymeric erosion, disentanglement, dissolution, swelling front movement, drug dissolution and diffusion through the polymeric matrix. These processes depend upon the interaction between the dissolution media, polymeric matrix and drug molecules, which can be significantly influenced by formulation variables and excipients. This study utilized mathematical parameters to evaluate the impacts of selected formulation variables and various excipients on the release performance of hydrophilic polyamide 6,10 (PA 6,10) monolithic matrix. Amitriptyline HCl and theophylline were employed as the high and low solubility model drugs, respectively. The incorporation of different excipient concentrations and changes in formulation components influenced the drug release dynamics as evidenced by computed mathematical quantities (t x%, MDT x%, f 1, f 2, k 1, k 2, and К F). The effects of excipients on drug release from the PA 6,10 monolithic matrix was further elucidated using static lattice atomistic simulations wherein the component energy refinements corroborates the in vitro and in silico experimental data. Consequently, the feasibility of modulating release kinetics of drug molecules from the novel PA 6,10 monolithic matrix was well suggested.

Construction and in vitro characterization of an optimized porosity-enabled amalgamated matrix for sustained transbuccal drug delivery.

This research focused on constructing and characterizing an optimized porosity-enabled amalgamated matrix (P-EAM) for sustained transbuccal drug delivery. An interphase, co-particulate, co-solvent, homogenization technique and lyophilization guided through a Box-Behnken experimental design was employed in the fabrication, characterization and optimization of 15 P-EAMs. The effects of varying factor levels on the characteristic in vitro physicochemical performances of the P-EAMs were explored. Formulations had an average weight of 128.44+/-3.48 mg with a dimensional size of 8mm by 5mm. Surface morphology showed varieties of pore structures, widespread distributions and uneven interconnectors. Satisfactory drug-loading was achieved (53.14+/-2.19-99.02+/-0.74%). Overall amount of drug released in 8h was measured by the MDT(50%) value which ranged between 22.50 and 225.00 min. Formulation demonstrated significant levels of ex vivo bioadhesive strength measured as detachment force (F(det)=0.964+/-0.015 to 1.042+/-0.025 N) and work of adhesion (omega(adh)=0.0014+/-0.00005 to 0.0028+/-0.00008 J). The potential of the P-EAMs to initiate and sustain ex vivo transbuccal permeation of drug was shown and measured as a cumulative value of between 25.02+/-0.85 and 82.21+/-0.57% in 8h. Formulations were mesoporous in nature with pore sizes ranging from 40 to 100 A characterized by the presence of interconnectors. Statistical constraints were simultaneously set to obtain levels of independent variables that optimized the P-EAM formulation.