Intravenous hydroxypropyl-beta-cyclodextrin (HPBCD): Biomarkers, efficacy, and impact of dosing and administration route on therapeutic index

Spray freeze-drying (SFD) is a novel technique for formulating dry powders, particularly for pulmonary drug delivery via dry powder inhalers (DPIs). Despite their low density and excellent aerodynamic properties, such powders are affected by high cohesiveness due to their surface properties. Sugars such as mannitol (MAN), trehalose, raffinose, and sucrose are commonly used in SFD. MAN is widely employed due to its high MAN—ice eutectic temperature—at which MAN and water (ice) form a stable eutectic mixture—and its crystallinity. However, crystallinity can impact the microparticles’ (MPs) cohesiveness, since MAN exhibits distinct polymorphs (α, β, δ) with peculiar properties. This study provides valuable insights for the development of DPI formulations by ensuring precise control over MAN polymorphism, ultimately enhancing formulation stability and performance. We introduced, for the first time, an intermediate freezing (IF) step within the SFD process to modulate MAN polymorphism, demonstrating its synergy with optimised storage temperature conditions. Furthermore, polyvinylpyrrolidone, 2-hydroxypropyl beta cyclodextrin, dextran, and polysorbate 80 were employed as polymorphism-controlling agents for MAN, contributing to the development of stable formulations with reduced particle cohesion and improved storage stability at room temperature. For the first time, this study shows that MAN polymorphism in SFD can be controlled to drive dry powder inhaler performance.

QSPR modeling of hydroxypropyl beta-cyclodextrin using reverse-degree-based molecular topological indices

ABSTRACT Depression affects millions globally, prompting the search for novel treatments. Natural compounds like spice oleoresins show promise due to their bioactive constituents. This study explores the use of Hydroxypropyl-beta-cyclodextrin (HPBCD) for nano-encapsulation to enhance the efficacy of pepper, turmeric, and chilli oleoresins in alleviating depression in a mice model. Chronic unpredictable mild stress (CUMS) was induced for 28 days, followed by administering nano-encapsulated oleoresins (25 mg/kg). Behavioural analyses revealed improved activity, while neurochemical studies showed increased serotonin and dopamine levels with reduced monoamine oxidase (MAO) activity. Western blot highlighted changes in BDNF, supported by histopathological evidence of neuroprotection. Biochemical assays indicated reduced oxidative stress, acetylcholinesterase activity, and enhanced catalase and superoxide dismutase levels. 16S rRNA sequencing revealed improved gut microbiota, with increased beneficial bacteria. Notably, nano-encapsulated chilli oleoresin exhibited the highest efficacy. These findings support the multi-targeted potential of nano-encapsulated spice oleoresins as complementary treatments for depression, addressing neurobiological and gut-related factors.

Abstract Background Recombinant human NELL-1 (rhNELL-1) is a potent osteogenic protein with therapeutic potential in regenerative medicine. A stable formulation is essential to prevent aggregation during production, filling, storage, and clinical use. Methodology A four-stage rational formulation strategy was used: (1) identify intrinsic aggregation risks of rhNELL-1; (2) screen polysorbate- and cyclodextrin-based formulations to enhance colloidal and conformational stability; (3–4) test lead candidates under agitation, freeze/thaw, pH shifts, and elevated temperature. Analytical techniques included PEG challenge, differential scanning fluorimetry (DSF), isothermal chemical denaturation (ICD), and dynamic light scattering (DLS). Aggregation was assessed via visible particles (VP), opalescence, subvisible particles (SVP, Micro Flow Imaging), SDS-PAGE, and ultra-high performance size exclusion chromatography (UP-SEC). Results rhNELL-1 was prone to self-association via hydrophobic and electrostatic interactions. Polysorbate 20 (PS20) and hydroxypropyl beta cyclodextrin (HPB-LB-BCD) improved protein stability. PS20 markedly reduced VP and SVP formation. While HPB-LB-BCD alone did not further reduce SVP beyond PS20, it enhanced thermal stress resistance. PS20 was more effective under agitation. Conclusions Two lead formulations containing potassium phosphate/Tris buffer, sorbitol, PS20, and HPB-LB-BCD demonstrated strong resistance to aggregation under multiple stresses. PS20 mitigated interfacial stress, while HPB-LB-BCD suppressed solution-phase aggregation, especially at high temperatures. This systematic approach offers a framework for stabilizing other aggregation-prone proteins.

Treatment with a positive allosteric AMPA receptor modulator ("ampakine") can improve respiratory muscle activation and bladder function after sub-acute (days) to chronic (weeks to months) spinal cord injury (SCI). Prior studies of SCI and excitotoxicity provide evidence that ampakines may also promote neuroprotection. We hypothesized that initiating daily low-dose treatment with the low-impact ampakine CX1739 acutely after SCI would be neuroprotective and promote recovery. Adult rats received unilateral 150 kydne C4 contusion; CX1739 (5 mg/kg, n = 12) or vehicle (hydroxypropyl beta-cyclodextrin, HPCD; n = 11) given 15 min post-SCI and daily for 14 days. Breathing was evaluated using whole-body plethysmography, and locomotion was evaluated using an open field test. Cervical spinal cords were stained with NeuN to identify neuronal soma, MCA-6H63 to identify degenerating axons, and Iba-1 to identify microglia and macrophages. No differences between the HPCD and ampakine groups were noted in neuronal counts, number of MCA-6H63 positive axons, or Iba-1 staining. Respiratory rate and tidal volume were similar between groups. Ampakine treatment, however, was associated with reduced open-field motor scores and increased relative risk of post-SCI complications. We conclude that ampakine CX1739 (5 mg/kg) given daily over 0-14 days post-SCI provides no discernible benefit, and acute ampakine treatment is contraindicated, in contrast to delayed dosing paradigms. Ampakine treatment should be reserved for the subacute and chronic SCI conditions, beyond the acute period of glutamate-related neurotoxicity. These results will be particularly important in determining the optimal timing of ampakine administration as CX1739 progresses in clinical trials.

Hydroxypropyl-Beta-Cyclodextrin (HP-BCD) inhibits SARS-CoV-2 replication by modulating intracellular lipid dynamics and preventing viral replication complex formation.

Wuzhuyu Decoction, a classical prescription recorded in the Treatise on Cold Damage Disorders(Shang Han Lun), exhibits poor compliance among pediatric patients due to its intense bitterness and pungency. There is an urgent need to screen suitable flavor-masking formulations and elucidate their underlying mechanisms. In this study, volunteer-based visual analog scale(VAS) scoring and functional near-infrared spectroscopy(fNIRS) were employed to evaluate different flavor-masking formulations for Wuzhuyu Decoction. The optimal formulation was identified as comprising 20 mg·mL~(-1) hydroxypropyl beta-cyclodextrin(HP-β-CD), 3 mg·mL~(-1) ι-carrageenan, 1.5 mg·mL~(-1) mogroside, and 0.015% peppermint oil. This formulation reduced the bitterness score of the decoction from 8.20(severely bitter) to 2.17(slightly bitter), and the pungency score from 5.40(distinctly pungent) to 1.64(mildly pungent), with improvement rates of 73.54% and 69.63%, respectively. The flavor-masking mechanisms were investigated using Fourier-transform infrared spectroscopy(FTIR), molecular docking, quantum chemical calculations, and lingual surface thermography. The results showed that HP-β-CD effectively reduced the free 6-gingerol content in the decoction, thereby mitigating pungent stimulation. Peppermint oil lowered the lingual surface temperature, thus weakening the burning sensation associated with pungency. Among four anionic polysaccharides(κ-carrageenan, ι-carrageenan, xanthan gum, and sodium carboxymethyl cellulose) at matched viscosity(5 581.13 ± 30.00) cp, only ι-carrageenan significantly reduced bitterness, lowering the bitterness score from 8.20 to 5.86. Quantum chemical analysis revealed that ι-carrageenan reduced the electron cloud density of the nitrogen atom in evodiamine via intermolecular electrostatic induction, thereby attenuating bitterness perception. Additionally, mogrosides contributed sweetness, helping to correct unpleasant tastes. Validation studies were performed using three classical bitter-pungent prescriptions(Huanglian Decoction, Banxia Xiexin Decoction, and Guizhi Shaoyao Zhimu Decoction) which demonstrated that the proposed formulation significantly improved their bitter-pungent sensory profiles. This study addressed the bitter-pungent taste characteristics of traditional Chinese medicine(TCM) decoctions by summarizing a scientific flavor-masking strategy, i.e., controlling pungency through encapsulation, suppressing bitterness via electrostatic induction, and compensating with sweeteners and aromatics. The findings advance flavor-masking techniques in TCM decoctions from empirical trial-and-error methods to evidence-based scientific approaches.

The uniform lethality of glioblastoma (GBM) with a survival of less than 2 years despite best available therapy is attributed to treatment resistance due to DNA repair mechanisms that drive disease relapse and tumor heterogeneity. One prognostic factor identified as a reliable biomarker for GBM sensitivity to temozolomide (TMZ) and radiotherapy (RT) is the overexpression of O6-methylguanine-methyl-transferase (MGMT) enzyme. Patients with active MGMT were found to receive little benefit from TMZ and RT. They represent a group of great unmet need with no treatment options that significantly improve survival. Recently, several preclinical and clinical studies suggest that the alcohol aversion drug, disulfiram (DSF), inhibited MGMT and improved the efficacy of TMZ in GBM when combined with copper (Cu). However, phase II trial showed that there was no significant survival benefit from oral Cu/DSF. Nevertheless, the major limitation of oral Cu/DSF has been delivery of fragile DSF to the in vivo system. To address this limitation, we developed a novel delivery system using 2-hydroxypropyl beta cyclodextrin (HPβCD) encapsulating the Cu complex of DSF’s active metabolite, diethyldithiocarbamic acid (DDC). It was determined that HPβCD stabilized Cu(DDC)2. In vitro cell culture study revealed that HPβCD-Cu(DDC)2 inhibited MGMT through the ubiquitin-proteasome pathway. Inhibition of MGMT activity in cell cultures vastly increased the alkylation-induced DNA double-strand breaks, cytotoxicity, and the levels of apoptotic markers like histone family member X (γ-H2AX), JNK-P and cleavage of Poly [ADP-ribose] polymerase 1 (PARP-1). Preliminary intravenous delivery of HPβCD-Cu(DDC)2 in combination with TMZ in an MGMT-positive patient derived orthotopic xenograft (PDOX) model demonstrated tumor size regression. HPβCD-Cu(DDC)2 targets MGMT-145-cysteine and its unique cytotoxic mechanism circumvents MGMT-mediated TMZ resistance. This novel delivery system shows promise for overcoming MGMT-mediated resistance in GBM, offering a potential new therapeutic strategy.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-14731-4.

Rational C onstruction of Hp-β-cd E nriched rGO R einforced Z inc O xide as an A ctive C atalyst for the E lectrochemical M onitoring of M elatonin in B iological S amples Chun-Wei Oub, Aravindan Santhana,b, Cheng-Han Wang b andKuo-Yuan Hwa a,b,c* aDepartment of Molecular Science and Engineering, National Taipei University of Technology, Taipei, Taiwan (ROC). bGraduate Institute of Organic and Polymeric Materials, National Taipei University of Technology, Taipei, Taiwan (ROC). cCollege of Engineering, National Taipei University of Technology, Taipei, Taiwan (ROC).Developing hydroxypropyl beta-cyclodextrin (Hp-β-cd) based reduced graphene oxide with metal oxide (zinc oxide) composite as a remarkably cost-effective electrochemical sensor with excellent stability and performance is a tough endeavor. The synthesized catalyst (Hp-β-cd/rGOs) will be an appropriate design for a sustained electrode material for the electrochemical detection of melatonin. Also, we have published works describing the functionalization of rGO and its combination with several other composites for various sensor applications. Melatonin (MTN), is an endogenous hormone in the brain that regulates our everyday circadian rhythm, hence its detection is a necessity that aids in regulating various health-related issues. The Hp-β-cd/rGOs/ZnOFs were first characterized to examine their physicochemical characteristics. The electrocatalytic performance of the Hp-β-cd/rGOs/ZnOFs-modified glassy carbon electrode (GCE) for MTN detection has been investigated using CV and DPV. A notable enhancement in both charge transfer rate and conductive properties was noted, which is attributable to the wrinkled sheet-like morphology of the Hp-β-cd/rGOs/ZnOFs material. The combined significances of Hp-β-cd/rGOs and ZnOFs with good electrocatalytic activity, high surface area, and improved active sites showed an extensive wide linear range and an impressive limit of detection (LOD) of 15 nM, indicating tremendous sensitivity in determining the presence of feasible interfering molecules. The Hp-β-cd/rGOs/ZnOFs tailored sensor demonstrated promising results when tested for real-time detection of melatonin in human serum samples. It demonstrated a remarkable recovery rate of 99 % for the investigation of real samples and can be utilized to develop commercially available electrochemical sensors with potential sensing features. Figure 1

Remdesivir was selected as a treatment for viral infections due to its efficacy as an antiviral agent against various RNA viruses such as Ebola and coronaviruses. The drug exerts its benefits during the later stages of viral infection, particularly post-fusion, endocytosis, translation, and proteolysis within host cells. It integrates into emerging viral RNA chains, disrupting transcription and ultimately inhibiting replication. However, its low water solubility poses limitations for clinical development. To enhance its solubility, current efforts focus on creating drug inclusion complexes using cyclodextrin derivatives. In this study, in silico techniques, including molecular docking and molecular dynamics simulations, were employed to investigate the molecular mechanisms and stability of remdesivir encapsulation using cyclodextrin derivatives. Various cyclodextrins were utilized, including beta-cyclodextrin, hydroxypropyl-beta-cyclodextrin (HPBCD), and sulfobutylether-beta-cyclodextrin (SBCD), docked against remdesivir. Molecular dynamics simulations were conducted in a water-saturated 1-octanol environment, a biphasic solvent system frequently used to mimic biological membrane conditions and assess solubility and partitioning behavior. Molecular docking results indicated that the complexes of remdesivir with HPBCD and SBCD exhibited the lowest binding energies of −10.69 kcal/mol and −8.34 kcal/mol, respectively. Furthermore, molecular dynamics simulations over 100 ns showed that these complexes maintained good stability. Analysis of molecular motion, RMSD, RDF, Rg, and SASA revealed increased water solubility and stability of the complexes. This evidence suggests that encapsulating remdesivir with HPBCD and SBCD can enhance its solubility.

The work involved taste masking of primaquine phosphate (PMQ), an intensely bitter drug used in the prevention and treatment of relapses of malarial infections caused by Plasmodium vivax and ovale. Drug and cation exchange resins viz, AmberLite™ IRP 64, 69, and 88 (IER 64, IER69, and IER88) were subjected to complex formation in 1:1 and 1:2 ratios using the shake flask method. Inclusion complexes of PMQ with hydroxypropyl beta cyclodextrin (HPBCD) were prepared to employ co-grinding, kneading, co-evaporation, and spray drying methods. Solid dispersions of PMQ with Eudragit E 100 (E 100) were prepared in various ratios by spray drying. In vitro, drug release studies of the composites were performed in 0.1N HCl and pH 6.8 phosphate buffer. The composites showing the least drug release in pH 6.8 buffer without compromising the release in an acidic medium were also evaluated for drug release in simulated salivary fluid (SSF). The selected composites were formulated into orally disintegrating tablets (ODTs) and subjected to human panel taste evaluation. PMQ-HPBCD spray-dried complex, PMQ-IER 69 (1:2) complex, and PMQ-E100 (1:4) dispersion exhibited drug release in decreasing order in SSF but > 85% release within 1h in an acidic medium. Hence, these composites were formulated into ODTs. The human panel tasting indicated the most acceptable taste of the ODTs comprising PMQ-E 100 dispersion followed by PMQ- IER 69 (2) complex, and lastly PMQ HPBCD complex. The PMQ-E100 dispersion-based ODTs could thus be a promising option for treating pediatric and geriatric patients with PMQ.

Poor drug entrapment, burst release, and variable drug release profiles are the most critical challenges associated with biodegradable-polymer-based microspheres. In this study, biodegradable-polymer-based microspheres were used to entrap an antiplatelet drug, eptifibatide, using a single-emulsion solvent evaporation method. Critical challenges associated with biodegradable-polymer-based microspheres were addressed by incorporating different additives in the drug or polymer phase. Additives such as hydroxy propyl beta cyclodextrins (HPβCD), carboxy methyl cellulose sodium (Na CMC), and trehalose were added to the drug phase to evaluate their impact on the entrapment and stability of eptifibatide. The effect of the addition of additives such as polyvinyl alcohol (PVA), polyethylene glycol-400 (PEG-400), and methoxy polyethylene glycol phospholipid dimyristoyl phosphatidylethanolamine (mPEG-2000-DMPE, Na) to the polymer phase on the release profile of eptifibatide was evaluated. The inclusion of HPβCD resulted in good drug entrapment and helped control the initial unwanted burst release. Including Na CMC increased eptifibatide entrapment from 75% to 95%. Trehalose helped prevent the degradation of eptifibatide during lyophilization, and including PVA and PEG-400 reduced the lag phase and led to a controlled-release profile. Thus, including additives in the formulation can effectively improve the drug load and address issues associated with biodegradable-polymer-based microspheres.

Excitotoxicity, which is defined as toxicity resulting from excess excitatory signaling, contributes to the secondary SCI cascade. In turn, this may cause neuronal loss beyond what results from the primary injury. Previous studies have reported that administering ampakines, which are positive allosteric modulators of AMPA type glutamate receptors, can mitigate the neuronal loss that occurs during excitotoxicity induced by administration of AMPA agonist or excitotoxic drugs (PMID: 11869032). Other work suggests that ampakines may be neuroprotective when initiated 7 days after SCI (PMID: 36764296). We hypothesized that a low dose of a “low impact” ampakine (CX1739) would mitigate neuronal loss in the mid-cervical spinal cord when initiated shortly after SCI. Adult (age 11 ± 1 weeks) Sprague Dawley (SD) rats received a right unilateral C4 contusion (impact force = 150 kdyne). A control group (n=5) consisted of spinal intact rats who received the same anesthetic and analgesic regimen. CX1739 (5mg/kg; n=7) or vehicle, hydroxypropyl beta cyclodextrin (HPCD; n=7) was administered 15-min post injury and then daily for 14 days. The cervical spinal cord was harvested, sectioned (20 um), and incubated with an antibody for neuronal nuclear protein (NeuN) to identify neurons. Tissues were imaged using the PhenoImager HT (Akoya Biosciences®) microscope NeuN-positive cells were counted in the vicinity of the lesion (C4-C6) using the Cellpose cellular segmentation algorithm (PMID: 33318659). Compared to spinal-intact tissue, the SCI caused the expected reduction in neuronal counts with the greatest reduction centered at the lesion epicenter. There was no evidence that CX1739 treatment had a neuroprotective impact. Neuronal counts across the lesion (C4-C6) were similar in the CX1739 and HPCD treated groups (p=0.59). Both groups were dramatically reduced relative to the spinal intact group (p<0.0001). We conclude that administering a low dose of ampakine CX717 beginning shortly after mid-cervical contusion injury has no detectable benefit on neuronal survival. 5R01HL138708-04 (DF), 5R01HL153140-03 (DF), 5T32HD043730-19 (AFF), Frank M Davis MD Chairman Emeritus Grant (AFF), 1K99NS133388-01A (SR) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Supramolecular interaction of ketoprofen with native and hydroxypropyl beta-cyclodextrin: Improved solubility and anti-inflammatory.

Abstract Glioblastoma (GBM) is a malignant glioma characterized by molecular heterogeneity and poor prognosis. GBM remains a uniformly lethal malignancy, with patient survival rarely exceeding two years despite the best available treatments. In clinical practice, about 60% of GBM patients have shown overexpression of O6-methylguanine-methyl-transferase (MGMT), an enzyme responsible for DNA repair, were found to receive little benefit from TMZ and represent a group of great unmet need with no chemotherapeutic agents that significantly improve survival. A key factor contributing to treatment resistance and disease relapse is the overexpression of MGMT. MGMT overexpression reduces the efficacy of standard therapies like temozolomide (TMZ) and radiotherapy (RT), leaving patients with active MGMT expressions in urgent need of new treatment strategies. The depletion of MGMT in tumors has been investigated as a strategy to increase TMZ and RT efficacies in resistant, MGMT-positive GBMs. Chemical depletion using O6-benzylguanine derivatives as MGMT inhibitors have been actively tested, but these compounds are associated with high hematologic toxicity. Recent studies have shown that disulfiram (DSF), an alcohol aversion drug, combined with copper (Cu), can inhibit MGMT and improve the response to TMZ in GBM. However, phase II clinical trials using oral Cu/DSF demonstrated no survival benefit, primarily due to the instability of DSF in vivo. To address this limitation, we developed a novel delivery system using 2-hydroxypropyl beta cyclodextrin (HPßCD) encapsulating the Cu complex of DSF's active metabolite, diethyldithiocarbamic acid (DDC). This HPßCD-Cu(DDC)2formulation stabilizes the complex, preventing degradation and reducing non-specific interactions in the bloodstream. In vitro studies revealed that HPßCD-Cu(DDC)2 inhibited MGMT through the ubiquitin-proteasome pathway. Inhibition of MGMT activity in cell cultures vastly increased the alkylation-induced DNA double-strand breaks (gama-H2AX), that are hallmark of TMZ effectiveness as supported by cytotoxicity and the increased levels of apoptotic markers, like JNK-P and cleavage of PARP-1. Systemic delivery of HPßCD-Cu(DDC)2 in MGMT overexpressed patient derived orthotropic xenograft resulted in depletion of MGMT with tumor size regression. Tumor burden has been evaluated within patient derived orthotropic rat models that represent high expression of MGMT followed by oral vs intravenous treatments. Citation Format: Meser M. Ali, Hamid Suhail, Mahesh Yadab, Ataur Rahman, James Snyder. Targeting DNA repair mechanism that leverages current standard of care interventions with a novel agent in glioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4484.

Abstract Bilastine (BLA) is a modern second – generation antihistamine employed to manage symptoms associated with allergic rhinoconjuctivitis and urticaria. However, it is very slightly soluble in water with low bioavailability, which affects its therapeutic action. The main objective of this research was to enhance the solubility and dissolution rate of BLA by complexation technique using beta cyclodextrin)β-CD) and its derivatives, hydroxypropyl beta cyclodextrin) HP-β-CD), methyl beta cyclodextrin(M-β-CD), and sulfobutyl ether beta cyclodextrin (SBE-β- CD) . Binary and ternary complexes using different hydrophilic polymers were prepared using kneading, solvent evaporation, co-grinding, and microwave methods. The resulting complexes were characterized for their percentage yield, drug content, solubility, and dissolution. The best complex was further characterized by XRD and FT-IR. The obtained results revealed that the ternary complex consisting of BLA, M-β CD, and soluplus ® (1mole /1mole / 5% w/w ) prepared by solvent evaporation method, exhibited the highest solubility (7.8 times more than the pure BLA) and the fastest release rate, where 90 % of BLA was released within the first 15 minutes at pH 6.8 with percentage yield of 89.3 % and 100 % drug content. Furthermore, the FTIR analysis confirmed the inclusion of BLA within the cavity of M-β CD. Additionally, the XRD diffractograms indicated the amorphous nature of the resulting complex

Introduction: The present study focuses on the solubility and dissolution rate enhancement of Brexpiprazole with Hydroxy Propyl β-cyclodextrin and succinic acid as a solubiliser for schizophrenia. Materials & Method: Brexpiprazole was obtained as a gift sample from CTX Life sciences, Sachin, Surat. Hydroxypropyl beta cyclodextrin was gifted by Good Health Pvt. Ltd Sachin, Surat. Binary and ternary complexes were prepared using three different methods and characterized using the fourier transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction and invitro dissolution studies. Results: It was observed that among different ratios of drug and polymer used, 1:5 ratio of drug and polymer for binary complex was found to be the optimized and solvent evaporation method gave the best results. The ternary complex was then prepared using this ratio in different concentration of succinic acid (0.25, 0.5 and 1 % w/w) and optimum concentration of succinic acid as a solubiliser was of 1 %. The drug release was found to be maximum 92 % as compared to binary complex. The fourier transform infrared spectroscopy, differential scanning calorimetry and X-ray diffraction results confirmed the formation of stable complex. Conclusions: It was concluded that ternary complex had maximum drug release of 92% at the end of 60 minutes resulting in solubility and dissolution rate enhancement.

Objective: This present research study was undertaken with the objective of formulating a fast-dissolving sublingual film of pre-solubilized bilastine. The aim was to overcome the need for acidic gastric media for the solubilization of bilastine, eliminating the concern of reduced bioavailability due to interaction with food and providing a faster onset of action, owing to the high vascularity in the sublingual region. Methods: Solubility enhancement of bilastine was achieved by inclusion-complex formation of bilastine and Hydroxypropyl Beta-Cyclodextrin (2-HP-β-CD). Fast-dissolving sublingual films were formulated by incorporating bilastine-2-HP-β-CD in the film prepared using the solvent casting method, wherein the sublingual film formulation was optimized using the Design of Experiments (DoE) approach by applying 23 factorial designs. The optimized sublingual film was evaluated. Results: Evaluation tests revealed that the optimized sublingual film possessed adequate flexibility and tensile strength. It exhibited a faster in vitro drug release of 97.41%, which was achieved in 7 min compared to a 35.77% in vitro drug release demonstrated by the pure drug-containing film. This indicates a 2.7-fold enhancement in dissolution with an average disintegration time of 41.66±0.57 s. The ex vivo permeation studies showed an in vitro drug release of 95.21%, indicating good permeation. Conclusion: Based on the research findings obtained, it is possible to conclude that the developed quick-dissolving sublingual film of bilastine possessed an enhanced dissolution profile and exhibited a faster onset of action. These results demonstrate the potential to avoid food interactions and improve patient compliance. Incorporating bilastine into sublingual films offers superior benefits over conventional oral formulations, such as circumventing hepatic first-pass metabolism and providing quick relief. Thus, it serves as a potential alternative for the treatment of chronic urticaria and allergic rhinitis.

Purpose: This study aimed to develop sustained-release triamcinolone acetonide (TA) formulations using lipid liquid crystals (LLCs) for ocular drug delivery and to characterize the designed formulations.Methods: Eighteen dispersed LLC formulations were prepared through a top-down approach, incorporating varying concentrations of TA and different proportions of glyceryl monooleate, deionized water, and pluronic F127. An additional formulation comprising TA: hydroxypropyl beta-cyclodextrin (HPβCD) complex was also developed to investigate the influence of HPβCD on the properties of the formulations. The formulations were evaluated for their rheological properties in room temperature using a rheometer, syringeability by passing them through a 27G needle, size measurements via dynamic light scattering (DLS), and morphology through polarized light microscopy (PLM). Furthermore, the prepared formulations were injected into a dialysis tube and placed in a phosphate buffer at pH 7.4 and 37 °C for in vitro release evaluation. Samples were taken at predetermined intervals and stored in a refrigerator until HPLC analysis. The percentage of Encapsulation efficacy and drug loading were evaluated using an indirect method. A reversed-phase HPLC method was employed to quantify the drug concentrations in the samples.Results: All selected formulations demonstrated acceptable parameters, including particle size (less than 200 nm), polydispersity index (PDI) ranging from 0.202 to 0.355, and zeta potential values between -14.3 and -32.8 mV. Additionally, the formulations showed good syringeability and achieved 100% drug release within 48 hours (except for the formulation containing HPβCD). PLM analysis revealed the presence of hexosomes and cubosomes, indicating that an increase in hexosomes contributed to a more uniform drug release from the formulations.Conclusion: Overall, the study findings suggest that liquid crystalline carriers can be a promising formulation for sustained ocular drug delivery of TA.