Optimization of QuEChERS method for determination of pesticide residues in vegetables and health risk assessment.

The present study focused on the optimization of the QuEChERS extraction method for the determination of 61 pesticide residues and associated health risk assessment in 144 samples of commonly consumed vegetables, viz., eggplant, cabbage, green chilli, okra, and tomato. The samples were collected between January and April 2022 from three different districts within Gujarat, India. The QuEChERS method was optimized and utilized for the extraction of samples. The samples were analyzed by UHPLC-q-TOF/MS and GC-MS/MS. The modified QuEChERS method was successfully validated, and the obtained results were satisfactory as per the 2021 SANTE guidelines. The residue analysis of the vegetable samples showed that about 4% of total samples contained single pesticide residues. Pesticide residues below the quantitation limit (BQL) were observed in eggplant, cabbage, and okra samples. In total, 15.62% (n = 5) samples of green chilli showed the presence of pesticides such as azoxystrobin, bifenthrin, cypermethrin, fenpropathrin, and propargite whereas 3% (n = 1) tomato samples contained cyfluthrin. In total, 97.22% of the samples had residues that were below the European Union Maximum Residue Limit (EU MRL). Two samples of green chilli had pesticide residues above EU MRL. The Hazard Index (HI) and Hazard Quotient (HQ) were used to assess the health risks associated with green chilli and tomato consumption. The HI and HQ values for adolescents and adults were found to be less than 1. The modified QuEChERS method was found to be easy and effective and can be implemented for routine sample analysis. The study revealed the presence of pesticide residues in tomato and green chilli samples. Further, the outcome provided information pertaining to current pesticide status, concluding that consumption of these commodities is unlikely to pose any health risk, though long-term monitoring studies focusing on dietary health risk assessment must be initiated.

Recent advancements in nanomaterial-mediated ferroptosis-induced cancer therapy: Importance of molecular dynamics and novel strategies.

Ferroptosis is a novel type of controlled cell death resulting from an imbalance between oxidative harm and protective mechanisms, demonstrating significant potential in combating cancer. It differs from other forms of cell death, such as apoptosis and necrosis. Molecular therapeutics have hard time playing the long-acting role of ferroptosis induction due to their limited water solubility, low cell targeting capacity, and quick metabolism in vivo. To this end, small molecule inducers based on biological factors have long been used as strategy to induce cell death. Research into ferroptosis and advancements in nanotechnology have led to the discovery that nanomaterials are superior to biological medications in triggering ferroptosis. Nanomaterials derived from iron can enhance ferroptosis induction by directly releasing large quantities of iron and increasing cell ROS levels. Moreover, utilizing nanomaterials to promote programmed cell death minimizes the probability of unfavorable effects induced by mutations in cancer-associated genes such as RAS and TP53. Taken together, this review summarizes the molecular mechanisms involved in ferroptosis along with the classification of ferroptosis induction. It also emphasized the importance of cell organelles in the control of ferroptosis in cancer therapy. The nanomaterials that trigger ferroptosis are categorized and explained. Iron-based and noniron-based nanomaterials with their characterization at the molecular and cellular levels have been explored, which will be useful for inducing ferroptosis that leads to reduced tumor growth. Within this framework, we offer a synopsis, which traverses the well-established mechanism of ferroptosis and offers practical suggestions for the design and therapeutic use of nanomaterials.

Unlocking the potential of nanocarrier-mediated mRNA delivery across diverse biomedical frontiers: A comprehensive review.

Messenger RNA (mRNA) has gained marvelous attention for managing and preventing various conditions like cancer, Alzheimer's, infectious diseases, etc. Due to the quick development and success of the COVID-19 mRNA-based vaccines, mRNA has recently grown in prominence. A lot of products are in clinical trials and some are already FDA-approved. However, still improvements in line of optimizing stability and delivery, reducing immunogenicity, increasing efficiency, expanding therapeutic applications, scalability and manufacturing, and long-term safety monitoring are needed. The delivery of mRNA via a nanocarrier system gives a synergistic outcome for managing chronic and complicated conditions. The modified nanocarrier-loaded mRNA has excellent potential as a therapeutic strategy. This emerging platform covers a wide range of diseases, recently, several clinical studies are ongoing and numerous publications are coming out every year. Still, many unexplained physical, biological, and technical problems of mRNA for safer human consumption. These complications were addressed with various nanocarrier formulations. This review systematically summarizes the solved problems and applications of nanocarrier-based mRNA delivery. The modified nanocarrier mRNA meaningfully improved mRNA stability and abridged its immunogenicity issues. Furthermore, several strategies were discussed that can be an effective solution in the future for managing complicated diseases.

Exploring modified chitosan-based gene delivery technologies for therapeutic advancements.

One of the critical steps in gene therapy is the successful delivery of the genes. Immunogenicity and toxicity are major issues for viral gene delivery systems. Thus, non-viral vectors are explored. A cationic polysaccharide like chitosan could be used as a nonviral gene delivery vector owing to its significant interaction with negatively charged nucleic acid and biomembrane, providing effective cellular uptake. However, the native chitosan has issues of targetability, unpacking ability, and solubility along with poor buffer capability, hence requiring modifications for effective use in gene delivery. Modified chitosan has shown that the "proton sponge effect" involved in buffering the endosomal pH results in osmotic swelling owing to the accumulation of a greater amount of proton and chloride along with water. The major challenges include limited exploration of chitosan as a gene carrier, the availability of high-purity chitosan for toxicity reduction, and its immunogenicity. The genetic drugs are in their infancy phase and require further exploration for effective delivery of nucleic acid molecules as FDA-approved marketed formulations soon.

Localized delivery of Erlotinib using liposomal gel formulations for the treatment of oral squamous cell carcinoma.

Oral cancer accounts for more than 350,000 cases worldwide with 90% of them being oral squamous cell carcinomas (OSCC). The current treatment modalities of chemoradiation have poor outcomes along with harmful effects to neighbouring healthy tissues. The present study aimed to deliver Erlotinib (ERB), locally at the site of tumor arising in the oral cavity. ERB was encapsulated in liposomal formulations (ERB Lipo) and optimized using full factorial, 32 experimental design. The optimized batch was then coated with chitosan to obtain CS-ERB Lipo and were characterized further. Both liposomal ERB formulations had size <200 nm and PDI < 0.4. Zeta potential was upto -50 mV for ERB Lipo and upto +25 mV for CS-ERB Lipo indicating stable formulation. Liposomal formulations were freeze dried and loaded into gel to study in-vitro release and chemotherapeutic evaluation. CS-ERB Lipo showed sustained release upto 36 h from gel as compared to control formulation. In-vitro cell viability studies showed potent anti-cancer activity on KB-cells. In-vivo studies showed better pharmacological efficacy in terms of tumor volume reduction for ERB Lipo gel (49.19%) and CS-ERB Lipo gel (55.27%) as compared to plain ERB Gel (38.88%) applied locally. Histology also revealed that formulation could alleviate dysplasia condition to hyperplasia. The locoregional therapy of ERB Lipo gel and CS-ERB Lipo gel thus show promising outcome in improving pre-malignant and early-stage oral cavity cancers.

Determination of multi-class pesticide residues in food commodities from Gujarat, India and evaluation of acute and chronic health risk.

An increasing concern for food safety has drawn attention to the overuse of pesticides, which pose a risk to public health. The present study determined 61 pesticide residues in 120 samples of cauliflower, green chili, cucumber, grapes, bananas and mangoes samples, and these were collected from markets in Ahmedabad, Gandhinagar, Surendranagar, Anand and Sabarkantha districts of Gujarat state, India. The samples were extracted and analyzed using ultra-high performance liquid chromatography-time of flight mass spectrometry (UHPLC-q-TOF-MS) and Gas chromatography-tandem mass spectrometry (GC-MS/MS). In addition, the health risk assessment associated with pesticide residues were evaluated by calculating the Hazard Quotient (HQ) and Hazard Index (HI), which indicate a value of less than 1 is safe for consumption. Out of 61 pesticide residues, 29 residues were detected in 107 samples; 68 samples showed multiple residues, and 39 samples found a single residue. Pesticides such as dimethoate, λ-cyhalothrin, fenvalerate, bifenthrin, and cyfluthrin were frequently detected in samples. HI in adults and adolescents confirmed a value less than 1 in cauliflower, cucumber, grapes and mango samples and greater than 1 in green chili and banana samples, respectively. The overall results depicted that, no considerable risk was observed in the selected food commodities. However, green chili and banana samples were found to exhibit marginal risk to human health. As a result, proper application, implementation of control plans, and continuous monitoring are required to prevent the risk and safeguard human health.

Human health risk assessment of pesticide residues in vegetable and fruit samples in Gujarat State, India.

The present study was initiated with the purpose to evaluate possible health risks associated with pesticide residues through consumption of vegetables and fruits by general population of Gujarat, India. A total of 1075 samples comprising of twelve different varieties of commonly consumed food commodities were collected from twenty-five divergent locations in Gujarat. The collected samples were extracted using QuEChERS method and analyzed for the presence of organophosphorus (OPs), organochlorine (OCs) and synthetic pyrethroids (SPs) pesticides using UHPLC-HR/MS, GC-µECD and GC-MS/SIM. The results indicated that 2.3% of vegetable and fruit samples showed the presence of pesticide residues exceeding maximum residue limits (MRLs). The results suggested that, detected residue levels in samples were within safe limits and their consumption will not pose any significant health risk to human. The outcomes present significant information regarding the status of vegetable and fruit contamination and pointed out the prerequisite for further studies with reference to monitoring of pesticides and other toxic contaminants in different samples for assessing cumulative health risk.

Long-acting formulation strategies for protein and peptide delivery in the treatment of PSED.

The invigoration of protein and peptides in serious eye disease includes age-related macular degeneration, choroidal neovascularization, retinal neovascularization, and diabetic retinopathy. The transportation of macromolecules like aptamers, recombinant proteins, and monoclonal antibodies to the posterior segment of the eye is challenging due to their high molecular weight, rapid degradation, and low solubility. Moreover, it requires frequent administration for prolonged therapy. The long-acting novel formulation strategies are helpful to overcome these issues and provide superior therapy. It avoids frequent administration, improves stability, high retention time, and avoids burst release. This review briefly enlightens posterior segments of eye diseases with their diagnosis techniques and treatments. This article mainly focuses on recent advanced approaches like intravitreal implants and injectables, electrospun injectables, 3D printed drug-loaded implants, nanostructure thin-film polymer devices encapsulated cell technology-based intravitreal implants, injectable and depots, microneedles, PDS with ranibizumab, polymer nanoparticles, inorganic nanoparticles, hydrogels and microparticles for delivering macromolecules in the eye for intended therapy. Furthermore, novel techniques like aptamer, small Interference RNA, and stem cell therapy were also discussed. It is predicted that these systems will make revolutionary changes in treating posterior segment eye diseases in future.

Betamethasone Dipropionate Nanocrystals: Investigation, Feasibility and In Vitro Evaluation.

Corticosteroids, such as betamethasone dipropionate (BMD), have been the mainstay in topical therapy as potent glucocorticoid receptor agonist with immune suppression, anti-proliferative, and anti-inflammatory effects. Moreover, they have poor skin penetration, which is a hurdle against its potential therapeutic benefits. In present investigation, nanocrystals as carrier for effective topical delivery of BMD were explored using wet milling as technique and polysorbate 80 as a non-ionic stabilizer. Upon optimizing different process parameters, promising results were observed at stabilizer concentration of 0.9% w/v having particle size analysis (PSA) and PDI as 284 nm and 0.299, respectively. These results were supported by the FTIR and PXRD spectra of BMD-API and BMD nanocrystals, suggesting strong crystal lattice structure of BMD being reduced due to milling. The reduction in particle morphology was evident from the FESEM images. The optimized batch of BMD nanocrystals was incorporated into Carbopol gel base, showing pH 6.2 ± 0.2 and viscosity 87.00 ± 5.2 Pa s at 25°C. A drug diffusion study using Franz diffusion cell proclaimed around ~86% BMD release from nanogel across the membrane. Also, it was observed that the BMD permeation across the skin was 2.39-fold higher with marketed formulation in contrast to BMD nanogel, suggesting prolonged drug release. The skin permeation flux with nanogel was at a much lower rate along with ~50.27% drug retention in different strata of skin, resulting in retention of drug nanocrystals. Thus, in nutshell the prolonged drug release from nanogel would fulfill the aim of once a day application and would aid in reducing the adverse events associated with repeated drug applications.

Surface modifications of gold nanoparticles: stabilization and recent applications in cancer therapy.

Gold nanoparticles (GNPs) are noble metal nanocarriers that have been recently researched upon for pharmaceutical applications, imaging, and diagnosis. These metallic nanocarriers are easy to synthesize using chemical reduction techniques as their surface can be easily modified. Also, the properties of GNP are significantly affected by its size and shape which mandates its stabilization using suitable techniques of surface modification. Over the past decade, research has focused on surface modification of GNP and its stabilization using polymers, polysaccharides, proteins, dendrimers, and phase-stabilizers like gel phase or ionic liquid phase. The use of GNP for pharmaceutical applications requires its surface modification using biocompatible and inert surface modifiers. The stabilizers used, interact with the surface of GNP to provide either electrostatic stabilization or steric stabilization. This review extensively discusses the surface modification techniques for GNP and the related molecular level interactions involved in the same. The influence of various factors like the concentration of stabilizers used, their characteristics like chain length and thickness, pH of the surrounding media, etc., on the surface of GNP resulting in stability have been discussed in detail. Further, this review highlights the recent applications of surface-modified GNP in the management of tumor microenvironment and cancer therapy.

Development and Optimization of Asenapine Sublingual Film Using QbD Approach.

Asenapine, an atypical antipsychotic agent, has been approved for the acute and maintenance treatment of schizophrenia and manic episodes of bipolar disorder. However, the extensive hepatic metabolism limits its oral bioavailability. Therefore, the objective of the current investigation was to develop sublingual film containing asenapine to enhance the therapeutic efficacy. Sublingual films containing asenapine were fabricated using polyethylene oxide and hydroxypropyl methylcellulose by solvent casting method. Design of experiment was used as a statistical tool to optimize the proportion of the film-forming polymers in order to establish the critical quality attributes of the drug formulation. The process was studied in detail by assessing risk of each step as well as parameters and material attributes to reduce the risk to a minimum. A control strategy was defined to ensure manufacture of films according to the target product profile by evaluation of intermediate quality attributes at the end of each process step. Results of optimized formulations showed rapid disintegration, adequate folding endurance, good percentage elongation, tensile strength, and viscosity. Besides, the results from the in vitro dissolution/ex vivo permeation studies showed rapid dissolution (100% in 6 min) and higher asenapine permeation (~ 80% in 90 min) through the sublingual epithelium. In vivo study indicates greater asenapine absorption (31.18 ± 5.01% of administered dose) within 5 min and was comparable with marketed formulation. In summary, the designing plan to develop asenapine formulation was successfully achieved with desired characteristics of the delivery tool for sublingual administration.

Tacrolimus encapsulated mesoporous silica nanoparticles embedded hydrogel for the treatment of atopic dermatitis.

Atopic dermatitis (AD) is a repetitive inflammatory skin disorder with limited treatment options. Innovative targeted therapies are gaining significant interest and momentum towards disease control including better ways to deliver drugs topically. Tacrolimus is one such compound which is used to manage moderate to severe AD without causing atrophy which is one of the common side effects of steroids. However, Tacrolimus suffers from poor solubility and retention in the skin when used alone in hydrogel. Therefore, we have prepared Tacrolimus loaded mesoporous silica nanoparticles (TMSNs) to overcome the issues related to its solubility and effective topical delivery. Mesoporous silica nanoparticles (MSNs) were synthesized using sol gel technique and surface functionalized using amino (-NH2+) and phosphonate (-PO3-) groups. Tacrolimus was loaded into MSNs and the particles were characterized for particle size (TEM and DLS), zeta potential (DLS), solubility studies, FTIR, TGA, XRD, BET and cytotoxicity studies. Water solubility of Tacrolimus was increased by 7 folds with phosphonate functionalized MSNs compared to free Tacrolimus. Further the TMSNs were incorporated in to carbopol gel, and the gel formulation was evaluated for various gel characterization tests (pH, spreadability, viscosity), in vitro tests (drug release, permeability studies) and in vivo tests (skin irritation study and efficacy studies) using 1-Fluoro-2,4-dinitrobenzene (DNFB) induced dermatitis in Balb/c mice. Results of in vitro and in vivo study showed that TMSNs loaded gel showed significantly higher amount of Tacrolimus retained (ex vivo - rat skin) and much higher reduction in ear thickness and improved histology (in vivo - in mice). Our data collectively suggest that MSNs incorporated hydrogel as a promising new formulation strategy for topical delivery of poorly soluble drugs.

Stimuli responsive and receptor targeted iron oxide based nanoplatforms for multimodal therapy and imaging of cancer: Conjugation chemistry and alternative therapeutic strategies.

Cancer being one of the most precarious and second most fatal diseases evokes opportunities for multimodal delivery platforms which will act synergistically for efficient cancer treatment. Multifunctional iron oxide magnetic nanoparticles (IONPs) are being studied for few decades and still attracting increasing attention for several biomedical applications owing to their multifunctional design and intrinsic magnetic properties that provide a multimodal theranostic platform for cancer therapy, monitoring and diagnosis. The review article aims to provide brief information on various surface chemistries involved in modulating IONPs properties to exhibit potential therapy in cancer treatment. The review addresses structural, magnetic, thermal and optical properties of IONPs which aids in the fabrication of efficient multimodal nanoplatform in cancer therapy. The review discussed the pharmacokinetics of IONPs and attributes influencing them. This review inculcates recent advancements in therapies, focused on tumor-microenvironment-responsive and targeted therapy along with their eminent role in cancer diagnosis. The concept of stimuli-responsive including endogenous, exogenous and dual/multi stimuli-based delivery platform demonstrated significantly enhanced anticancer therapy. Several therapeutic approaches viz. chemotherapy, radiotherapy, immunotherapy, hyperthermia, gene therapy, sonodynamic therapy, photothermal, photodynamic-based therapy along with biosensing and several toxicity aspects of IONPs have been addressed in this review for effective cancer treatment.

Hot-Melt Extrusion: An Emerging Technique for Solubility Enhancement of Poorly Water-Soluble Drugs.

The solubility of the drug is a significant aspect to be considered during manufacturing of pharmaceutical products. Poor aqueous solubility of drugs imparts depleted bioavailability. In this regard, several techniques are available for enhancing drug solubility or dissolution. However, only few of them are scalable and industrially applicable. Hot-melt extrusion (HME) is one such technique that has been widely used in the industry. It is a single-step, continuous manufacturing, and scalable method that has proved successful in improving the solubility of poorly soluble drugs. This review highlights the numerous pharmaceutical applications of HME, such as formulations of sterile implants, taste masking of unpleasant drugs, cocrystallization, salt formation, sustained and controlled release formulations, etc. It also describes various hydrophilic and hydrophobic carriers utilized in HME. This review also briefly discusses the recent advances in HME and gives an update on the currently available marketed products. The opportunities and challenges in future development of pharmaceutical products by HME technique are also discussed.

Emerging Nanomedicines for the Treatment of Atopic Dermatitis.

Globally, the prevalence of Atopic dermatitis (AD) is significantly increasing and affecting around 20% of population including children. Complex interactions amongst abnormality in epidermal barrier function, environment, infectious agents and immunological defects are considered as key factors in the pathogenesis of AD. Although the role of oxidative stress has been studied in some skin diseases, investigation of the same in AD is intermittent. Calcineurin inhibitors and/or topical corticosteroids are currently available; however, it causes atrophy of the skin, burning sensation, and systemic side effects which leads to poor patient compliance. These limitations provoke the strong need to develop an innovative approach in managing AD. Nanomaterials for effective drug delivery to skin conditions such as AD have attracted a lot of attention owing to its ability to encapsulate, protect, and release the cargo at the diseased skin site. However, there are lots of unmet challenges especially in terms of development of non-toxic formulations and clinical translation of established nanomedicines in the form of accessible products. Numerous formulations have emerged as carrier for poorly soluble and permeable drugs, viz., lipidic, polymeric, metal, silica, liposomes, hydrocarbon gels and this field is evolving. This review is intended to provide an insight incidences associated with pathophysiology of AD and challenges with existing treatments of AD. Focus is kept on reviewing current development and emerging nanomedicines for effective treatment of AD. The review also inculcates merits of several nanomedicines in overcoming challenges of existing products and its future implications.

Molybdenum-based hetero-nanocomposites for cancer therapy, diagnosis and biosensing application: Current advancement and future breakthroughs.

In recent years, there have been significant advancements in the nanotechnology for cancer therapy. Even though molybdenum disulphide (MoS2)-based nanocomposites demonstrated extensive applications in biosensing, bioimaging, phototherapy, the review article focusing on MoS2 nanocomposite platform has not been accounted for yet. The review summarizes recent strategies on design and fabrication of MoS2-based nanocomposites and their modulated properties in cancer treatment. The review also discussed several therapeutic strategies (photothermal, photodynamic, immunotherapy, gene therapy and chemotherapy) and their combinations for efficient cancer therapy along with certain case studies. The review also inculcates various diagnostic techniques viz. magnetic resonance imaging, computed tomography, photoacoustic imaging and fluorescence imaging for diagnosis of cancer.

Cationic biopolymer functionalized nanoparticles encapsulating lutein to attenuate oxidative stress in effective treatment of Alzheimer's disease: A non-invasive approach.

Present investigation explores cationic biopolymer core/shell nanoparticles (Chitosan@PLGA C/SNPs) for delivering carotenoids to brain via intranasal route for supressing oxidative stress in Alzheimer's disease (AD). The prepared C/SNPs exhibited particle size less than 150 nm with more than 80% of entrapment efficiency. Surface morphology confirmed uniform coating of shell (chitosan) over core PLGA NPs and suggested spherical nature and homogenous dispersion of C/SNPs. In-vitro release study demonstrated sustained release of lutein while C/SNPs permeation enhancement was confirmed by ex-vivo diffusion study. The study also investigated effect of cationic-shell with respect to anionic-core NPs on biocompatibility, cellular uptake, uptake mechanism, reactive-oxygen species (ROS) generation, ROS scavenging activity, blood-brain-barrier (BBB) permeation. The cellular uptake revealed enhanced internalization of nanoparticles via caveolae-mediated endocytosis. In-vitro co-culture model of BBB demonstrated efficient passage for C/SNPs through BBB. Antioxidant assay demonstrated significant ROS scavenging activity of C/SNPs. In-vivo pharmacokinetic and bio-distribution was performed along with in-vivo toxicity and stability. In-vivo toxicity demonstrated absence of any significant toxicity. Photo and thermal stability confirmed protection of lutein by C/SNPs. C/SNPs were highly deposited in brain following intranasal route. The obtained results demonstrate the potential application of cationic C/SNPs for attenuating oxidative stress in brain for effective AD therapy.

Formulation of Chitosan Stabilized Silver Nanoparticle-Containing Wound Healing Film: In Vitro and In Vivo Characterization.

A wound indicates a discontinuity in the epithelial integrity of the skin along with structural and functional disruption of the underlying normal tissue. The study focused on chitosan stabilized silver nanoparticles (CH-AgNP) further incorporated in a chitosan-based (CH-AgNP-CHF) film for wound healing. Dual advantages of chitosan as a wound-healing agent in addition to the antimicrobial property of CH-AgNP nanoparticles was explored. Based on preliminary trials, 1-2% w/v chitosan as film former, 15-25% w/v glycerin as plasticizer and Teflon as casting surface was selected. The optimized CH-AgNP-CHF had tensile strength 1.39 ± 0.009 N/mm2, % Elongation 33.33 ± 1.634, 76.66 ± 0.584% degree of swelling, WVTR of 2024.43 ± 32.78 gm.m-2 day-1 and 1144.57 ± 13.45 gm.m-2 day-1 after 24 h and after 21 days respectively. The CH-AgNP-CHF reported highest % inhibition of 62.22 ± 0.91 against Escherichia coli as compared to chitosan solution, chitosan film and CH-AgNP solution. Based on in vivo animal study, CH-AgNP-CHF showed highest wound closure rate at 3rd, 5th, 7th, 14th and 21st day to indicate better and faster wound healing compared to marketed SilverKind® Nanofine gel, blank chitosan film and sterile gauze treated group (Control). Thus, CH-AgNP-CHF is more effective alternative for wound healing.

Improvement of oral bioavailability of carvedilol by liquisolid compact: optimization and pharmacokinetic study.

Low aqueous solubility is one of the major reasons for the poor clinical efficacy of carvedilol in oral therapy. The aim of the present investigation was to evaluate the potential of liquisolid compact technique to enhance the dissolution rates of carvedilol and thereby the bioavailability. Liquisolid compacts were prepared using polyethylene glycol 400, Neusilin US2 and Aerosil 200. Experimental design and optimization was carried out by applying a 32 factorial design (batches D1-D9) to examine the effects of independent variables (amount of load factor and the excipient ratio) on dependent variables (angle of repose and % drug release). Differential scanning calorimetry and X-ray diffraction studies suggested transformation of carvedilol to amorphous in D6, a key factor responsible for dissolution rate improvement. This effect was evidenced in the dissolution data of D6 (>95% drug dissolved in 30 min) where the drug release kinetics followed Weibull model. It was observed that the amount of load factor influenced angle of repose and excipient ratio affected drug dissolution of liquisolid compacts. Pharmacokinetic profile of D6 was prominent, demonstrating greater carvedilol absorption than the control in rats. The observed increase in systemic bioavailability of carvedilol AUC0-∞ (p < 0.005) by liquisolid compact is likely due to the improvement in drug solubility. The data observed in the current study demonstrated that the liquisolid compact technique could be a promising strategy to enhance the bioavailability of carvedilol and could be used in oral therapy. Graphical abstract.