Permeation Enhancers Research Articles

Buccal Absorption of Biopharmaceutics Classification System III Drugs: Formulation Approaches and Mechanistic Insights

Buccal drug delivery emerges as a promising strategy to enhance the absorption of drugs classified under the Biopharmaceutics Classification System (BCS) Class III, characterized by high solubility and low permeability. However, addressing the absorption challenges of BCS Class III drugs necessitates innovative formulation strategies. This review delves into optimizing buccal drug delivery for BCS III drugs, focusing on various formulation approaches to improve absorption. Strategies such as permeation enhancers, mucoadhesive polymers, pH modifiers, ion pairing, and prodrugs are systematically explored for their potential to overcome challenges associated with BCS Class III drugs. The mechanistic insight into how these strategies influence drug absorption is discussed, providing a detailed understanding of their applicability. Furthermore, the review advocates for integrating conventional buccal dosage forms with these formulation approaches as a potential strategy to enhance absorption. By emphasizing bioavailability enhancement, this review contributes to a holistic understanding of optimizing buccal absorption for BCS Class III drugs, presenting a unified approach to overcome inherent limitations in their delivery.

Recent Advances in Transdermal Drug Delivery Systems

Transdermal drug delivery systems (TDDS), particularly transdermal patches, represent a significant advancement in pharmaceutical technology, offering non-invasive drug administration through the skin. These systems provide controlled release mechanisms and improved therapeutic outcomes. The evolution of TDDS has effectively addressed various limitations of conventional drug delivery methods, by escaping first-pass metabolism and maintaining steady plasma drug concentrations. Technological innovations have introduced sophisticated materials and formulation strategies, including advanced polymer matrices, smart delivery systems, and novel permeation enhancers. The integration of nanotechnology has expanded the scope of transdermal delivery, enabling the administration of previously unsuitable drug molecules. Current knowledge of skin structure and its barrier function has led to improved transdermal patch designs incorporating microemulsions, nanocarriers, and smart polymers. Advanced technologies such as microneedles, iontophoresis, and sonophoresis have significantly improved drug permeation capabilities. Marketed formulations demonstrate successful implementation of these technologies, while ongoing research continues to optimize characterization methods and delivery mechanisms. The development of more effective and patient-friendly transdermal systems has resulted in improved therapeutic outcomes and enhanced patient compliance, marking a significant advancement in drug delivery technology. Recent innovations suggest a promising future for transdermal delivery systems in addressing complex therapeutic challenges and meeting diverse patient needs.

Combining SNAC and C10 in oral tablet formulations for gastric peptide delivery: A preclinical and clinical study.

Current oral formulations of macromolecules including peptides typically rely on single permeation enhancer (PE) to promote absorption and thus bioavailability. In this work, we combined two PEs, namely sodium N-[8-(2-hydroxybenzoyl) amino] caprylate (SNAC) and sodium caprate (C10), in one tablet formulation to potentially gain a synergistic effect for enhanced gastric absorption of a GLP-1 analogue and a PCSK9 inhibitor. Permeability tests on a gastric organoids-based cell model showed that the combination of SNAC and C10 can significantly improve peptide permeability compared to either SNAC or C10 alone. Tablet formulations were then designed, adjusting the total PE amount, relative ratio between SNAC and C10, and the peptide dose. To facilitate drug and PE release, a diluent was added. Upon oral administration in beagle dogs, the lead formulations made of SNAC/C10/diluent demonstrated higher bioavailability than either SNAC, SNAC/diluent and C10/diluent formulations for both peptides. Finally, the SNAC/C10/diluent formulation with PCSK9 inhibitor was tested in human, where it displayed similar bioavailability to the SNAC/diluent reference, thereby suggesting a low translatability between pre-clinical and clinical data when C10 was involved. This may be attributed to the difference in physiology, gastric pH environment as well as C10 concentration and colloidal form in the gastric lumen between dogs and humans. Hence, additional studies are needed for a better understanding of the clinical translation of C10-based peptide formulations.

Current Technological Advances in Mucoadhesive Buccal Drug Delivery Systems and Their Therapeutic Applications

Buccal drug delivery has emerged as a promising route of administration, offering distinct advantages over conventional oral delivery systems. The unique physiological characteristics of the buccal mucosa, including rich vascularity and relatively high permeability, make it an attractive site for both local and systemic drug administration. Bioadhesive formulations have revolutionized buccal drug delivery by ensuring prolonged contact with the mucosal surface, thereby enhancing drug absorption and bioavailability. Recent developments in polymer science have introduced novel mucoadhesive materials, including thiolated polymers, lectins, and stimuli-responsive systems, which demonstrate superior adhesion properties and controlled release characteristics. Various formulation approaches, such as films, tablets, patches, and hydrogels, have been developed to optimize drug delivery through the buccal route. These systems incorporate permeation enhancers, enzyme inhibitors, and novel drug carriers to overcome the biological barriers associated with buccal delivery. The application of nanotechnology has further advanced the field, introducing nanostructured formulations that exhibit enhanced mucoadhesion and improved drug permeation. Current research focuses on developing intelligent delivery systems that respond to physiological triggers and maintain therapeutic drug levels. Understanding the critical factors affecting bioadhesion, including polymer characteristics, environmental conditions, and physiological variables, has led to the development of more effective formulations. The integration of modern analytical techniques and quality control measures ensures the development of stable and efficient buccal delivery systems and improves patient compliance and therapeutic outcomes

OPTIMIZING TRANSDERMAL PATCH FORMULATION FOR ENHANCED DELIVERY OF RIVAROXABAN: A COMPREHENSIVE DESIGN OF EXPERIMENTS APPROACH

Objective: To optimize Trans Dermal Patches (TDPs) of rivaroxaban using Poly Vinyl Pyrrolidone (PVP K30) and Hydroxypropyl Methyl Cellulose E50(HPMC E50) as hydrophilic polymers, Propylene Glycol(PG) as a plasticizer, and permeation enhancer. Methods: TDPs were crafted using a solvent casting technique with a 2-level, 3-factor factorial design. These patches were assessed for thickness, folding endurance, in vitro drug release, drug content, and moisture uptake and loss. An 8-stage diffusion cell apparatus facilitated in vitro drug release testing. The independent variables were HPMC E50, PVP K30, and PG. The change in the concentration of these independent variables resulted in the optimization of the transdermal patch. The dependent variables were the thickness, folding endurance, and in vitro diffusion. Results: The patch thickness ranged from 0.311±0.3 to 0.334±0.6. Folding endurance ranged from 58±0.7 92±6. The in vitro drug release ranged from 52.36% to 95.58%. The percentage drug content ranged from 83.58±0.4 to 95.26±0.5. The percentage of moisture content absorbed ranged from 21.36±0.13% to 25.54±0.26%. The percentage of moisture lost ranged from 1.01% to 2.31%. Conclusion: PG increased the release of rivaroxaban because it permeated the membrane. HPMC E50 is highly soluble. Thus, rivaroxaban patches are potentially suitable transdermal drug delivery systems.

Enhancement of transdermal permeation of phycobiliprotein by nanodispersion with lipopeptide from Bacillus subtilis

Enhancement of transdermal permeation of phycobiliprotein by nanodispersion with lipopeptide from Bacillus subtilis

Matrimid®/LaNi5 mixed matrix membranes for selective hydrogen separation from industrial waste gas streams

This study reports the synthesis, characterization, and evaluation of Matrimid®/LaNi5 mixed matrix membranes for selective hydrogen separation from industrial waste gas streams. Through a combination of experimental investigation and modelling, hydrogen absorption in LaNi5 intermetallic compounds and its impact on separation performance were explored. It was observed that the composite membranes exhibit significant enhancement in hydrogen permeation compared to pristine Matrimid® membranes. The results showed that Matrimid®/LaNi5 membranes deliver 5 times higher H2 permeability (107 Barrer) and higher selectivity (H2/CO2: 14.5, H2/N2: 83.5, H2/CH4: 78.5 and H2/CO: 84.5). Furthermore, hydrogen permeation flux modelling in Matrimid®/LaNi5 elucidated the contribution of each transport mechanism with high regression coefficients (> 0.92) and within ± 15% error. Moreover, the results demonstrate the capability of Matrimid®/LaNi5 membranes to surpass Robeson upper bound for H2/CO2 while it is almost reached for H2/N2 and H2/CH4 separations, highlighting the potential of these new membranes for industrial-scale applications.

Enabling simultaneous CO2 and water vapor removal by MOF-801/Pebax mixed matrix membranes: Molecular simulation and experimental study

Dehydration and CO2 removal are two important gas separation processes. An efficient membrane enabling simultaneous reduction of water vapor and CO2 levels from humid gas streams, such as natural gas and power plant flue gas, may advance these processes. In this study, a water-harvesting metal-organic framework, MOF-801, was synthesized with an average particle size of 120 nm, which was then dispersed in a Pebax matrix to fabricate mixed matrix membranes (MMMs). The potential of the MOF-801 as a filler in MMMs was evaluated for water and CO2 separation from CO2/N2 and CO2/CH4 mixed gas streams. Compared with the neat Pebax membrane, 70% enhancement in the water permeability was achieved for an MMM of 20 wt.% MOF loading at 10 bar with a humid feed composition of CO2/CH4. A considerable CO2/N2 separation factor (108) and CO2 permeability (270 Barrer) were also obtained, exceeding the Robeson upper bound at both dry and humid states. A molecular simulation study was performed to reveal the adsorption sites in the MOF lattice and favorable interactions with gases. Interestingly, competition between gas components close to the Zr atom was observed, which is the favorable site for both CO2 and water. Competitive adsorption was found to be the dominating transport mechanism for the selective transport of CO2 and H2O in MOF-801, revealing the role of MOF-801 in MMMs for CO2 and water vapor separation under both humid and dry conditions.

Comparing effects of terpene-based deep eutectic solvent and solid microneedles on skin permeation of drugs with varying lipophilicity

Transdermal delivery of therapeutic molecules is often hindered by the properties of the skin, with the stratum corneum serving as the primary permeation barrier. To overcome this barrier, the integrity of the stratum corneum can be modified by chemical permeation enhancers, such as deep eutectic solvents (DESs), or by mechanically impairing the skin with microneedles (MNs). However, a systematic comparison between these strategies is currently lacking. Hence, this study examined the potential of DESs and MNs to promote the permeation and retention of drugs with varying lipophilicities – specifically, the hydrophilic drug metronidazole (logP ∼ 0), the moderately lipophilic drug lidocaine (logP ∼ 2.3), and the highly lipophilic drug clotrimazole (logP ∼ 5). A mixture of menthol and thymol was selected as a model terpene-based DES and delivery vehicle, while a DermaPen equipped with solid MNs was used to mechanically impair the skin. Permeation rates of model drugs applied to the skin with either DES, MNs, or both were compared to the rates determined for the drugs applied in control vehicles. Both strategies were found to compromise the skin barrier function, but their permeation-enhancing effect was dependent on the lipophilicity of tested model drug. The DES was most effective for the hydrophilic drug metronidazole, while the MNs were more effective in increasing the permeation of the highly lipophilic drug clotrimazole. For the moderately lipophilic drug lidocaine, neither the DES nor microneedles increased its permeation rate, as the drug permeated through the skin well on its own. Notably, the combination of both enhancement strategies did not result in significantly better permeation rates of the drugs compared to the individual approaches. In conclusion, both the terpene-based DES and solid MNs are effective strategies to enhance drug permeation through the skin, but our results suggest that the choice of strategy should be dictated by the drug’s lipophilicity. Moreover, from a permeation-enhancing perspective, there is no benefit in combining these two strategies.

Effect of Natural Oils as Permeation Enhancer for Transdermal Delivery of Telmisartan

Aim of the present study was to determine the feasibility of natural oils as permeation enhancers for the development of a transdermal delivery system of telmisartan. The penetration-enhancing potential of olive oil and clove oil on in-vitro permeation of telmisartan across shed snake skin was studied. The patches were evaluated for their physicochemical characteristics, in-vitro drug release, and in-vitro permeation studies. The system containing hydroxypropyl methylcellulose and Eudragit L-100 (6:4) as matrix forming agents and dibutyl phthalate (20%) as plasticizer was selected as the best formulation for incorporation of natural oils as penetration enhancers. All transdermal patches were found to be uniform with respect to physical characteristics. Formulation (T7) containing 10% olive oil was found to be a promising natural permeation enhancer for transdermal delivery of telmisartan with the greatest cumulative amount of drug permeated (1536 μg/cm2) over 24 h. The studies indicated that the feasibility of transdermal delivery of telmisartan as a patch is likely to suffice the therapeutic requirement.

Optical Clearing of Ex Vivo Adipose Tissue.

The paper focuses on the development of technology of adipose tissue optical clearing using different complex hyperosmotic optical clearing agents and tissue permeability enhancers. To quantify optical clearing efficiency, reduced scattering coefficient was estimated from the ex vivo spatially resolved backreflectance measurements using a multi-distant fiber optical device. Tissue morphology modification was monitored with the help of histological studies. Kinetics and efficiency of the optical clearing were evaluated for ex vivo abdominal fat tissue at action of dimethyl sulfoxide, diatrizoic acid, metrizoic acid, sucrose, and fructose solutions accompanied by tissue permeability enhancers, such as various modes of fractional laser microablation and sonophoresis and their combinations. Histological studies allowed us to find agents that cause minimal morphological changes of the adipose tissue. Maximal optical clearing efficiency of 83.5% was observed for the samples subjected to action of the fructose-ethanol solution during 90 min in combination with gentle modes of fractional laser microablation and sonophoresis.

Programmable NIR Responsive Nanocomposite Enables Noninvasive Intratympanic Delivery of Dexamethasone to Reverse Cisplatin Induced Hearing Loss.

Local intratympanic drug delivery to the inner ear possesses significant otological clinical promise as cisplatin-induced hearing loss (CIHL) therapy, inducing significantly less side effects than systemic drug delivery. However, the multiple detoured barriers, round window membrane (RWM) and poorly controlled drug release hinder successful non-invasive drug delivery through intratympanic administration (IT). Here, a novel near-infrared (NIR) responsive nanocomposite functionalized with saponin, denoted gold nanorod@dexamethasone-mesoporous silica-saponin (AuNR@DEX-MS-saponin, NPs/DEX), is developed to enhance RWM permeation and to control the drug release spatiotemporally. First, the physiochemical properties and release profile of the synthesized nanocomposites are assessed, after which the biocompatibility of the nanocomposites and oto-protection against CIHL are shown in vitro and in vivo. The findings demonstrated that DEX is delivered to the inner ear with high efficiency through IT, due to the permeation enhancement effect of the nanocomposite. Moreover, the nanocomposite with low dose of DEX is highly effective in recovering CIHL, attenuating hair cell loss, and alleviating synaptic ribbon damage. These findings provide insight into NIR-responsive local delivery for inner ear illnesses.

Evaluation of physical and chemical modifications to drug reservoirs for stimuli-responsive microneedles.

Hydrogel-forming microneedle (MN) arrays are minimally-invasive devices that can penetrate the stratum corneum, the main barrier to topical drug application, without causing pain. However, drug delivery using hydrogel-forming MN arrays tends to be relatively slow compared to rapid drug delivery using conventional needles and syringes. Therefore, in this work, for the first time, different physical and chemical delivery enhancement methods were employed in combination with PVA-based hydrogel-forming MN arrays. Using a model drug, ibuprofen (IBU) sodium, the designed systems were assessed in terms of the extent of transdermal delivery. Iontophoresis (ITP) and heat-assisted drug delivery technology were investigated as physical permeation enhancement techniques. Ex vivo studies demonstrated that the ITP (0.5mA/cm2)-mediated combination strategy significantly enhanced the transdermal permeation of IBU sodium over the first 6h (~ 5.11mg) when compared to MN alone (~ 1.63mg) (p < 0.05). In contrast, heat-assisted technology showed almost no promoting effect on transdermal delivery. Furthermore, IBU sodium-containing rapidly dissolving lyophilised and effervescent reservoirs, classified as chemical modification methods, were prepared. Both strategies achieved rapid and effective ex vivo IBU sodium permeation, equating to ~ 78% (30.66mg) and ~ 71% (28.43mg) from lyophilised and effervescent reservoirs, respectively. Moreover, in vivo pharmacokinetic studies showed that the IBU sodium plasma concentration within lyophilised and effervescent groups reached a maximum concentration (Cmax) at 4h (~ 282.15µg/mL) and 6h (~ 140.81µg/mL), respectively. These strategies not only provided rapid achievement of therapeutic levels (10-15µg/ml), but also resulted in sustained release of IBU sodium for at least 48h, which could effectively reduce the frequency of administration, thereby improving patient compliance and reducing side effects of IBU sodium.

Numerical simulation of hydro-shearing stimulation in the enhanced geothermal system at the Utah FORGE site

Hydro-shearing using low injection rates to stimulate the fractured geothermal reservoir for permeability enhancement. In this work, a series of 3D thermo-hydro-mechanical (THM) coupled simulations were run to investigate the hydro-shearing processes in enhanced geothermal system (EGS). In our model, natural fractures were considered according to the borehole televiewer image results. The enhancement of reservoir permeability was calculated using an empirical model derived from the hydro-mechanical coupling experiments. The THM coupled model was calibrated by reproducing the field monitoring data at the Utah FORGE site. The artificial reservoir volume and its permeability enhancement were investigated during injection test on well 58–32. The modelling results proved that hydro-shearing stimulation does not require the injection pressure to exceed the in-situ minimum principal stress. The hydro-shearing stimulation mechanism is controlled by the water injection induced reservoir cooling and pore pressure increase. For the given injection conditions at well 58–32, the artificial reservoir volume was estimated at about 67,000 m3. The maximum enhancement of reservoir permeability occurs in the vertical direction, thus using horizontal wells is beneficial for geothermal development at this site. The results presented in this work were beneficial for engineers to understand the hydro-shearing stimulation method.

Permeability Enhancement Induced by Fracture Shear Dilation During Close-Range Coal Seam Mining

The advance of the working face in coal seams alters the local stress field and may give rise to fractures in the vicinity of the excavation. In this study, a constitutive model in which damage is defined as a function of volumetric strain was established and utilized in a numerical model to prognosticate the fracture development around the excavation. The predicted fractures that emerged in the overlying rock mass were found to exhibit hybrid characteristics. A permeability model was also constructed, taking into account both tension- and shear-induced fracture development. The permeability increase of the upper adjacent coal seam is most notable within 40 m from the goaf boundary. As the working face progresses, the permeability of the upper adjacent coal seam is further enhanced while that of the lower adjacent coal seam remains unaffected. The permeability at the goaf boundary is high and reaches its maximum at the rear of the working face, indicating that for the permeability change, the effect of shear-induced dilation plays a more crucial role than that of pressure-dependent compaction. This study can be used to guide the design of coal seam methane drainage for the mining of closely spaced coal seams.

Aceclofenac delivery through polymeric nanoparticles loaded with transdermal hydrogel against rheumatoid arthritis

Hydrogels have gained attention in drug delivery systems for their ability to encapsulate nanoparticles, providing sustained and targeted release. In this study, polymeric nanoparticles (NPs) of aceclofenac (ACE) were loaded into a carbopol-based hydrogel to overcome problems associated with the conventional treatment concerning rheumatoid arthritis (RA). Polymeric NPs of ACE were fabricated via the nanoprecipitation method and incorporated into a Carbopol 934-based hydrogel with a permeation enhancer (PE). Furthermore, ACE-NPs was characterized and subjected to in vitro and ex vivo analyses, which revealed a sustained release (20 % drug release at pH 5.5 and 40 % release at pH 7.4) and the desired permeation flux (1200 μg/cm2) of the ACE-NP-loaded hydrogel with PE after 24 h. The optimized nanoparticles had a particle size of 141.1 nm and an entrapment efficiency (EE) of 87 %. XRD and FTIR further supported the structural and compositional analysis of the ACE-NPs. The physicochemical properties of the ACE-NPs loaded hydrogel with PE were also characterized. An in vivo study was carried out on a CFA-induced RA mice model. The behavioral parameters were investigated, and supportive histopathological and radiological data were recorded. These findings suggest that ACE-NPs loaded hydrogel is a promising treatment for RA.

Microstructural Evolution and Damage Mechanism of Water-Immersed Coal Based on Physicochemical Effects of Inorganic Minerals.

Coal seam water injection technology enables seam permeability enhancement and facilitates outburst risk reduction. This study investigated the microscale effects of water infiltration on coal and the evolution mechanisms of its mechanical properties. To this end, we systematically analyzed dynamic changes (such as mineral composition, pore structure, and mechanical performance) in coal soaked for various durations using X-ray diffraction, low-field nuclear magnetic resonance (NMR), and uniaxial compression testing. The results indicate: (1) the coal NMR T2 spectrum displays three characteristic peaks, corresponding to rapid water absorption, uniform transition, and stabilization stages of soaking traditionally divided according to peak area variation trends. (2) The coal strength decreases with progressive soaking, influenced by water content, pore volume, mineral composition, etc. Its compressive strength and elastic modulus drop by 22.4% and 19.5%, respectively, compared to the initial values. (3) The expansion of clay minerals during immersion reduces average pore size. In contrast, quartz particle displacement, pore water movement, and soluble mineral dissolution increase pore volume, reducing the overall structure strength. (4) The dominant factors driving the degradation of mechanical properties vary across immersion stages, including water content and specific mineral concentration. This work offers new insights into how hydraulic technology alters coal seams, providing theoretical support for optimizing water injection strategies in the seam.

Enhancing agrochemical delivery in citrus leaves with geraniol: a promising strategy for controlling huanglongbing (HLB).

Citrus huanglongbing (HLB) is a devastating disease in citrus, caused by Candidatus Liberibacter asiaticus (CLas), which primarily resides in the phloem where chemicals cannot effectively reach, posing a significant challenge in controlling HLB. To address these challenges, plant essential oils (EOs), widely used as transdermal enhancers and known for their benefits for plant tissues, were investigated for their potential to enhance chemical permeation. In this study, seven EOs - eugenol, carvacrol, eucalyptol, geraniol, linalool, cinnamaldehyde, and d-limonene - were evaluated for their potential to enhance chemical penetration into citrus leaves. Preliminary screening with tracer methods revealed that geraniol provided the greatest enhancement of permeation, achieving the deepest and broadest distribution into the spongy tissue of the citrus leaf. The permeation levels of rhodamine B and crystal violet through the cuticular layer were elevated from 0.55 mg L-1 and 0.11 mg L-1 to 20.04 mg L-1 and 7.14 mg L-1, respectively, by the addition of geraniol. Further validation through high-performance liquid chromatography-mass spectrometry (HPLC-MS) confirmed that the penetration of fludioxonil and tetracycline into citrus leaf tissues was enhanced by 15.07-fold and 20.43-fold, respectively. In planta experiments confirmed that adding geraniol to tetracycline and oxytetracycline via foliar application eliminated CLas bacteria in HLB-affected citrus more efficiently than controls. Our study underscores the potential of geraniol as an effective EO-based permeation enhancer for combating HLB. By significantly improving the delivery and efficacy of bactericidal treatments, geraniol offers a promising strategy for managing this catastrophic citrus disease, potentially transforming the approach to controlling HLB. © 2024 Society of Chemical Industry.

Estimation of Scattering Properties Modifications Caused by InVivo Human Skin Optical Clearing Using Line-Field Confocal Optical Coherence Tomography.

The image contrast and probing depth of optical methods applied to invivo skin could be improved by reducing skin scattering using the optical clearing method. The aim of this study was to quantify, from line-field confocal optical coherence tomography (LC-OCT) 3D images, the modifications of skin scattering properties invivo during optical clearing. Nine mixtures of optical clearing agents were used in combination with physical and chemical permeation enhancers on the human skin of three healthy volunteers. Scattering coefficient and anisotropy factor of the epidermis and the upper dermis were estimated from the 3D LC-OCT images of skin using an exponential decay model of the in-depth intensity profile. We were able to demonstrate a decrease in epidermal scattering (down to 33%) related to optical clearing, with the best results obtained by a mixture of polyethylene glycol, oleic acid, and propylene glycol.

Insights of physicochemical structure changes of bituminous coal with acidification-assisted controlled electric pulse through SEM, XRD and FTIR

Controlled electric pulse (CEP) cracking coal effectively enhances its permeability, but a high coal breakdown voltage (BV) can result in technical difficulties. To address this problem, the method of using HCl solution to improve the electrical conductivity of coal was proposed. The effects of HCl on coal BV were investigated, and the microstructural changes in coal were analyzed through scanning electron microscopy, X-ray diffraction, and Fourier-transform infrared spectroscopy. Compared with raw coal, the BV of acidified coal decreased significantly. The crushing degree of the coal samples was clearly enhanced with an increasing HCl concentration. Some internal coal minerals were acidified and dissolved, the aromatic layer spacing (d002) increased and the layer sheet stacking height (Lc) decreased, and the crystal structure was damaged. When acidified coal was broken down, numerous internal pores and cracks appeared, active coal groups were shed, the aliphatic hydrocarbons and oxygen-containing functional group contents increased, surface activity was reduced, and the hydroxyl content was reduced, which was conducive to rapid gas desorption. Acidification effectively reduces the BV of coal and improves the cracking and permeability enhancement effect of coal by CEP action.