Search

Abstract: Clay materials are widely used in drug delivery systems due to their unique characteristics. Montmorillonite is a major component of bentonite and it has a large surface area, better swelling capacity, and high adsorption capacity. The modification of natural bentonite could improve its sorption ability for new emerging applications. Recent advancements in the polymer-silicate composite have novel biomedical applications in drug delivery, tissue regeneration, wound healing, cancer therapy, enzyme immobilization, diagnostic and therapeutic devices, etc. Perspective view of the montmorillonite-polymer composite as a pharmaceutical carrier in drug delivery systems has been discussed in this review. Different types of modification of montmorillonite for the development of pharmaceutical formulations have also been documented. Many challenges in clay nanocomposite systems of polymer of natural/synthetic origin are yet to be explored in improving antimicrobial properties, mechanical strength, stimuli responsiveness, resistance to hydrolysis, etc. Drug interaction and binding capability, swelling of clay may be carried out for finding possible applications in monitoring delivery systems. Pharmaceutical properties of active drugs in the formulation could also be improved along with dissolution rate, solubility, and adsorption. The clay-incorporated polymeric drug delivery systems may be examined for a possible increase in swelling capacity and residence time after mucosal administration.

Investigation on the larvicidal potential of Elettaria cardamomum (L.) Maton rhizome extracts against filarial vector, Culex quinquefasciatus Say, was undertaken with crude concentrations 0.1-0.5 per cent and 40, 50, and 60 ppm of each of petroleum ether, hexane and ethyl acetate rhizome extracts revealed that first instar larvae were most susceptible to crude rhizome extract with 100 per cent mortality at 0.5% after 24 hrs of exposure. Among three solvent extracts, ethyl acetate extract showed maximum mortality (96.66±3.33%) at 60 ppm after 72 hrs of exposure. LC50 values of larvicidal bioassays by crude rhizome extract were 0.1002, 0.0794, 0.1275 and 0.6334 ppm for 1st, 2nd, 3rd and 4th instars larvae after 72 hrs of exposure, respectively and LC50 values for larvicidal bioassays by petroleum ether, hexane, and ethyl acetate rhizome extracts were 48.3629, 40.9613 and 37.0282 ppm against 3rd instar larvae after 72 hrs of exposure, respectively. Preliminary phytochemical analyses of the rhizome extracts showed presence of secondary metabolites. Non target organisms, tadpoles of frog and 4th instar larvae of Chironomus circumdatus, were not affected by the crude as well as ethyl acetate rhizome extracts. Larvicidal efficacy of the rhizome extracts of E. Cardamomum against Cx. quinquefasciatus mosquito species has been reported first time.

Proliferative retinopathy is described as a progressive neovascularization in the inner surface of the retina or vitreous, which subsequently threatens vision by causing retinal detachment or vitreous hemorrhage. Reactive oxygen species generation and its related vasoproliferative factor up regulation play a major role in progression of the disease. The present study focuses on Carr induced reactive species generation with its related vasoproliferative factor up regulation and ameliorative activity of AML. Biochemical estimation of catalase, lipid peroxidation, hypoxia inducing factor (HIF-1α) and guanyl-s-transferase (GST) were done. AML treated group showed significant increase in catalase enzyme, guanyl-s-transferase and significantly reduced the lipid peroxidation. Western blotting assay showed a significant decrease in HIF-1α in AML treated group. The progression of PR alters the endogenous cell signalling thus causing havoc in retinal cells. Therefore, it could be hypothesized that use of AML can be a new detection method for therapeutic strategies to prevent blindness in PR.

Ocular drug delivery in hydrogel forming film form has several benefits over conventional dosage forms. An ophthalmic anti-inflammation study was undertaken using topically applied aspirin in a hydrogel film formulation. A hydroxypropyl methylcellulose (HPMC) matrix film formulation was prepared by the solvent casting and evaporation technique by taking triethanolamine (TEA) as a plasticizer. Ex vivo corneal permeation as well as anti-inflammatory potential of aspirin was studied on carrageenan induced rabbit eye model. Moisture uptake was found to be in the range of 17.1 and 19.1 % for all the film formulations. The film with the higher HPMC content exhibited both increased moisture uptake and amount of swelling. Among the formulations, the swelling order was found to increase with increasing amount of HPMC in the film. Presence of the hydrogel matrix forming polymer sustained the drug release and corneal permeation for more than 6 h and controlled the process by the diffusion mechanism. The signs of carrageenan induced acute inflammation was inhibited completely within just 2 h of placing the film in the rabbit eye whilst the positive control continued showing redness and increased tear secretion. Aspirin ocular film formulation could be utilized for ocular anti-inflammation for an extended period of time with better patient compliance.

Natural gum tamarind is a plant polysaccharide extracted from seeds endosperm of the plant, Tamarindus indica Linn. Thin film of the gum was prepared by direct compression method. The prepared film was investigated for the effect of pH and temperature on solvent uptake property of film by gravimetric method. Different swelling parameters such as mass swelling ratio (MSR), equilibrium swelling ratio (ESR), equilibrium swelling ratio (ESw) and the equilibrium water content (EWC) were studied. It was found that swelling parameters were influenced by different pH and temperature conditions. The results suggested that the water content in equilibrium state was similar to body fluid. The gum converted to a high viscous gel of pseudo plastic characteristics in different pH conditions and the mechanism of continuous diffusion of solvent molecules into tablet during swelling was a non fickian and followed a second order kinetics.

Vildagliptin (VID) is a dipeptidyl peptidase-4 (DPP-4) inhibitor used in controlling blood glucose level in type 2 diabetes. Vildagliptin improves beta cells function and is also suggested to effectively control the inflammation. The possible ocular anti-inflammatory property of vildagliptin has been explored using topically applied plasticized ocular film formulation. Film formulation was prepared by solvent cast and evaporation method using triethanolamine (TEA), dimethyl sulphoxide (DMSO), and polyethylene glycol 400 (PEG 400) as the plasticizer in HPMC hydrogel matrix base. Anti-inflammatory study was carried out in the carrageenan induced ocular rabbit model. Analytical methods confirmed that the drug was present almost in completely amorphized form in the film formulation. Level of hydration, swelling and erosion rate of the film played the controlling factor in the process of drug release, ocular residence and permeation. Maximum swelling rate of 363 h−1 has been shown by VHT compared to other formulation of VHD and VHP (174 and 242 h−1 respectively). Film containing DMSO exhibited highest in vitro release as well as ex vivo ocular permeation. Film formulation has shown a fast recovery of ocular inflammation in contrast to the untreated eye after inducing inflammation. Plasticized vildagliptin hydrogel film formulation could be utilized in the management and control of ocular inflammation particularly with diabetic retinopathy after proper clinical studies in higher animal and human individuals.

The crystallization technique has been established as a cost-effective and simple approach to improve the dissolution rate and oral bioavailability of poorly soluble drugs. This study was carried out to study the effect of some selected hydrophilic polymers such as methyl cellulose, hydroxypropyl methylcellulose (HPMC), polyvinyl alcohol, and carboxymethyl cellulose on the crystal behavior and dissolution properties of celecoxib (CLX), a common nonsteroidal anti-inflammatory drug. Structural and spectral characteristics of crystallized CLX have been studied by Fourier transform infrared (FTIR) spectroscopy, diffraction scanning calorimetry (DSC), and X-ray diffraction (XRD) analysis. From FTIR and DSC analysis, no significant shifting of peaks or appearance of any new peaks (for polymers) were observed, which indicated the absence of any major interaction between drug and polymers as well as the absence of polymers in the final crystallized product of CLX. The XRD analysis showed a change in crystalline morphology to some extent. The dissolution rate of crystallized CLX in the presence of polymers (particularly with HPMC) was significantly improved compared with plain CLX. The improved dissolution profile of the experimental CLX crystal products could be an indication of improved bioavailability of CLX for better clinical outcome.

The objective of the present work was to investigate the effect of various hydrophilic polymers, such as hydroxypropylmethyl cellulose, methyl cellulose, carboxymethyl cellulose and poly vinyl alcohol, on the in vitro dissolution property of ibuprofen (IBU) crystallized from aqueous polymeric solutions. By using the solvent-change technique, IBU crystal products were produced in the presence of the selected polymers. The results showed that in the presence of polymers, the crystallization yield of IBU was higher than that of pure drug crystals (absence of polymer). SEM photographs revealed visible changes in the crystal morphology in the presence of polymers. The FTIR spectra of the crystallized IBU (polymer-treated) showed a shift of the acid- -dimer peak from 1718 to 1721 cm-1 but the absence of specific peaks for polymers. An XRD study further confirmed the absence of polymers in the crystallized IBU as no specific peaks were observed for the polymers. A higher percentage of cumulative drug release was reported for the polymeric-treated IBU crystals than that of plain IBU. Further in vivo studies are warranted to establish the in vitro?in vivo correlation for future technology transfer of the formulation.

Crystal engineering is an integral part of the drug development research. Crystal forms can modify the physicochemical properties of the parent drug molecule. The present work was aimed at the synthesis and characterization of crystalline product of lamotrigine (LT), an U.S. Food and Drug Administration approved anti-epileptic drug, with citric acid (CA) to improve its release in gastric region and oral absorption. The crystalline products of LT?CA were developed by solvent evaporation method using ethanol-water as the solvent system. Appearance of new characteristic peaks in the FTIR spectra for the crystal products indicated formation of new crystal state. In DSC thermogram, melting point of the experimental crystal products was different than that of the pure drug. Further, formation of new crystalline phase was confirmed from XRD data through the identification of new sharp peaks for the selected crystal products. A higher cumulative percentage of drug release was observed for the crystal products than for the free drug within 60 min of drug release in simulated gastric fluid. However, in vivo studies are warranted for the future technology transfer of the product at industrial scale.

Budesonide, a glucocorticosteroid is generally used to treat chronic inflammation and asthma. Hepatic first-pass metabolism and poor solubility are the major causes of its limited oral bioavailability. Present work was undertaken for the preparation of hydrogel film formulation with cyclodextrin complexation of budesonide containing quaternary surfactant for possible enhancement of mucosal permeation. FTIR study confirmed drug-polymer hydrogen bonding. Almost complete amorphization of the drug was pronounced by SEM, DSC and XRD studies. The film containing benzalkonium and hydroxypropyl beta-cyclodextrin exhibited in vitro dissolution and mucosal permeation to the highest extent of 87.2 and 95.8 % respectively in contrast to the others. Film formed hydrogel in aqueous mucin and enhanced the mucosal tissue residence time due to the mucoadhesive nature of the polymer. Acute inflammation in the rabbit eye was controlled within 3 h by applying the film in the cul-de-sac. The presence of cyclodextrin and quaternary surfactant brought about significantly improved drug release and mucosal permeation compared to their absence in the HPMC film. Hydrogel formed in aqueous mucin enhanced the mucosal residence time and controlled acute inflammation in the rabbit eye within 3 h after topical application.

BACKGROUND: Macitentan blocks endothelin receptors in order to control the pulmonary arterial hypertension (PAH). Oral administration of macitentan is associated with painful urination and troubled breathing. OBJECTIVES: Formulated macitentan hydrogel film was used for examining the control of intraocular pressure, and the effect of surfactant and cosurfactant was studied. METHODS: Macitentan ocular film formulation has been prepared in hydroxypropyl methylcellulose (HPMC) matrix system using different surfactant/co-surfactant system, and intraocular pressure was monitored on normotensive rabbit eyes after application in the cul-de-sac. RESULTS: The solid state characterization of the film indicated amorphisation of macitentan and no issues regarding major incompatibility was observed. Combination of surfactant, co-surfactant and hydrophilic co-solvent systems in the said films markedly improved the drug release and mucosal tissue permeation. Presence of PEG and Transcutol significantly improved ex vivo corneal permeation of MP and MT respectively compared to other films. Transcutol (MT) exhibited greatest difference among the formulations by improving the vesicular bilayer fluidity and reducing the mucosal tissue barrier facilitating the transcorneal diffusion. A combination of diffusion and erosion control behavior was observed in drug release and corneal permeation of the films due to the balanced liquid penetration and polymeric chain relaxation rate. MP and MT films were used for further in vivo studies to achieve possible effective and prolonged control of intraocular pressure. In vivo study has revealed the reduction in intraocular pressure upto about 23 % when tested on normotensive rabbit model. The films has managed to lower the IOP upto 3 h. CONCLUSION: Developed macitentan hydrogel film containing Transcutol (MT) could have a high potential for the control and management of ocular hypertension after topical application. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40199-021-00428-2.

‘Balarista’ is an important Ayurvedic arista formulation containing twelve crude drugs among which Sida cordifolia and Withania somnifera are the two major drugs. The Ayurvedic Formulary of India mentions various usages of Balarista, but it is mainly used in the treatment of rheumatoid arthritis. This study deals with the evaluation of pharmacognostic and physico-chemical properties of all incorporated drugs along with the HPLC and GC–MS analysis of the two main drugs. The macroscopic, microscopic, powder microscopy and physico-chemical parameters of different drugs were assessed according to the Ayurvedic Pharmacopoea of India. The scanning electron microscopic study, fluorescence analysis and powder behavior studies of various drugs in powder form were also carried out. The quantification of vasicine and total withanolides were analyzed in chloroform extract of Sida cordifolia and Withania somnifera root by HPLC method. Further, presences of other phytoconstituents were also confirmed by GC–MS analysis. The macroscopical, organoleptic, histological, powder characteristics and scanning electron microscopic images of various drugs revealed the important diagnostic features. The physico-chemical, fluorescence analysis and powder behavior characteristics provided useful tools to differentiate them from the adulterants. The HPLC analysis detected percentage of vasicine and total withanolide (withanoside IV, withanoside V, withaferin A, 12-Deoxy withastramonolide, withanolide A and withanolide B) in Sida cordifolia and Withania somnifera root respectively. GC–MS analysis identified fifty bioactive compounds in both the drugs. The pharmacognostical, physico-chemical and chromatographic assessment of these medicinally important plant drugs could be helpful for their authentication and in ensuring the quality of Balarista formulation.

Background: Viral infection caused by Hepatitis B is transmitted by permucosal or parenteral exposure and also one of the prime causes of hepatocellular carcinoma and liver cirrhosis. Objectives: M-cell targeting acid-resistant oral vaccine delivery have been formulated for immunization against Hepatitis B infection. Methods: Cationic solid lipid nanoparticles (cSLNs) were prepared utilizing solvent injection technique. Hepatitis B surface antigen (HBsAg) loaded alginate coated cSLNs were anchored with lipopolysaccharide (LPS). SDS-PAGE was performed to evaluate acid degradation protection of prepared formulation. Induction of immunity produced by prepared nanoparticle for Hepatitis B was determined on female Balb/c mice followed by ELISA assays for assessing anti-HBsAg IgG/IgA antibodies in mucosal fluids. Results: Sustained release of HBsAg (60.66 %) has been exhibited from alginate coated cSLNs in comparison to cSLNs without alginate coating (97.72 %) after 48 h. The production of anti-HBs titer in intestinal, salivary and vaginal secretions was 3.41 IU/ml, 3.1 IU/ml and 2.51 IU/ml respectively in comparison to the control group. Integrity of the M-cells has been maintained after binding with SLN, and oral administration delivered the antigen to the desired site of gut. Conclusion: It was found effective in producing antibodies in mucosal immunization against Hepatitis B virus. So, this formulation could be used as a promising alternative preexisting vaccine to prevent Hepatitis B infection.

Carrageenan induced oxidative stress develops retinal damage and increases lipid peroxidation. Glycation of the lens proteins increases modified proteins and may affect the lens structural integrity and opacification, after increasing glucose concentration in the lens. Trimetazidine (TZ) has been reported to have cytoprotective anti-ischaemic activity after systemic administration in an animal model. Trimetazidine ophthalmic film formulation has been prepared using HPMC as the hydrogel-forming polymer. The cytoprotective role of trimetazidine has been studied on carrageenan-induced retinal damage of rat eye by histologicaland Malondialdehyde (MDA) assay applying sterilized film formulation. Trimetazidine solution was used in combination with a high concentration of glucose solution (55 mM) for examining the protective effect from cataract formation. Formulation showed controlled and extended ophthalmic permeation of the drug for about 5 h. Damage of retinal cells in the ganglionic layer has been decreased significantly in the trimetazidinetreated group. Drug treated control group also showed significant disappearance of pyknotic cells. The addition of trimetazidine to the glucose medium practically retarded the lens opacification by reducing the over-production of reactive oxygen species (ROS) in increased sugar concentration. Presence of trimetazidine probably decreased the drop of protein level in lens under stressed condition and greater preventive effect has been noticed with TZ concentration of 240 µg/ml rather than 120 µg/ml. Trimetazidine ophthalmic film formulation could prevent retinal damage and cataract formation.

The global pandemic of COVID-19 is progressing rapidly across the world and declared as health emergency. The novel Coronavirus can cause severe lower respiratory tract infections primarily in geriatric, immunocompromised persons, infants and patients with comorbidities, or genetic disorders. Few Emergency Use Authorizations (EAUs) have been granted by FDA and other regulatory bodies with an aim to repurpose the existing approved medicines to fight the disease, and till date no specific treatment methodologies or preventive measures are available. At present, numerous medications which are already approved for other therapeutic indications, as well as the new medications, are undergoing clinical trials for the evaluation of safety and efficacy against COVID-19 infection. These therapeutic ranges include antimalarial, antiviral, steroids, convalescent plasma containing antibodies, and immune modulators, etc. Nevertheless, the primary focus is on preventive care and currently more than hundred potential vaccine candidates are under development by leading biotech companies across the globe which are at different phases of clinical development. Lipid based mRNA delivery, DNA delivery and mAbs are the most advanced technologies being embraced besides whole-virion inactivated vaccine, attenuated live vaccine, non-replicating viral vector-based vaccine, protein single unit vaccine and multiunit vaccine. This review focuses on the current progress in drug delivery systems of COVID-19 vaccine across industries, academics, and government funded research institutes with a special focus on the synthetic mRNA-based lipid nanoparticle (LNP).

Hydration behavior of hydrogel-based polymeric film possesses great importance in mucosal drug delivery. Modified Lag phase sigmoid model was used for the investigation of hydration of the film. Kaolin incorporated HPMC K100LVCR (HL) and K100M (HH) films containing dexamethasone as a model drug have been prepared for studying swelling kinetics. Swelling of HL and HH films was decreased with the gradual increase of kaolin content and HH of higher viscosity has shown higher value than HL matrix. Kaolin also inhibited the film erosion process. Mathematically modified lag phase sigmoid model demonstrated similarity of the predicted swelling content with the observed value. High R2 and small RMSE value confirmed the successful fitting of the modified lag phase sigmoid model to the experimental data of swelling content. τ value similar to the observed one was obtained. This modified model could be reliable enough for estimating hydration process in food grains, food packaging films etc.

Analysis of the binding interactions of ibuprofen and silicified-microcrystalline cellulose (SMCC) has been undertaken. Co-processing of ibuprofen with SMCC was carried out by solid state ball milling, and aqueous state equilibration followed by freeze drying to investigate the effect of silicified-microcrystalline cellulose on ligand. Molecular docking study revealed that ibuprofen formed complex through hydrogen bond with microcrystalline cellulose (MCC) and silicon dioxide (SiO 2 ); the binding energy between MCC and SiO 2 , and ibuprofen and SMCC were found as -1.11 and -1.73 kcal/mol respectively. The hydrogen bond lengths were varying from 2.028 to 2.056 A. Interaction of Si atom of SMCC molecule with Pi-Orbital of ibuprofen has shown the bond length of 4.263 A. Significant improvement in dissolution of ibuprofen has been observed as a result of interaction. Binary and ternary interactions revealed more stabilizing interactions with ibuprofen and SMCC compared to SMCC formation.

Recent developments and collaborations of pharmaceutical manufacturers, hospitals, and government funded research bodies using 3D printing technology have been highlighted for the management of the healthcare crisis 3D printing is a process of converting virtual 3D models developed by computer aided design into physical forms upon addition of material layer-by-layer (also known as additive manufacturing) This 3D printing is supposed to revolutionize significantly the healthcare system in the coming years This process involves a tailored deposition of biomaterials layer by layer such as polylactic acid (PLA), polyvinyl alcohol (PVA), or other suitable pharma-grade polymers, copolymers, and their combinations to formulate three-dimensional custom designs with controlled architecture and composition Food and Drug Administration (FDA) is currently thinking on regulation to ease the import restrictions for products intended for the detection and diagnosis of COVID-19 to ensure the timely availability of test kits

Titanium dioxide can adhere with human epithelial cells and have good tolerability. Present work has been undertaken to explore the influence of TiO2 on mucosal permeation of aceclofenac. Mucosal permeation of aeclofenac solution containing TiO2 has been carried out. In fourier transform infrared spectrosopy (FTIR), the intensity of the peaks has decreased along with the increase of TiO2 content in the formulation indicating a possible binding between drug and TiO2. Melting enthalpy has been decreased with the increased content of TiO2 in the solid. The status of crystal strain and dislocation density of TiO2 and aceclofenac in the solid state formulation has also been evaluated from Xray Diffraction data using Debye-Scherrer’s equation. Mucosal permeation of aceclofenac has shown sustained effect for more than 20 h in presence of titanium dioxide. Titanium dioxide could be used in designing formulation for sustaining mucosal aceclofenac delivery after performing risk assessment study.

Mucoadhesive type ocular film has been prepared for studying the anti-inflammatory potential of amlodipine (AML) on carrageenan-induced rabbit model and the effect of sulphobutyl-ether-beta-cyclodextrin on corneal permeation was tested. Hydroxypropyl methylcellulose (HPMC) ocular film was prepared after complexation of amlodipine with β-cyclodextrin, (BCD), hydroxypropyl β-cyclodextrin (HPCD), and sulfobutylether β-cyclodextrin (SBCD). The film without cyclodextrin showed a maximum swelling, and erosion to the highest extent. Both drug release and permeation were highly diffusion controlled and highest improvement was observed with SBCD due to increased dissolution, compared to other formulations with or without cyclodextrin. Highest binding energy and highest extent of amorphization were noticed in the SBCD film formulation. Improved amlodipine release in-vitro and ocular permeation were found by the HPMC film formulation after complexation of the drug with cyclodextrins wherein SBCD exhibited both to the highest extent. Binary and ternary systems molecular docking studies confirmed the lowest energy of binding between amlodipine and BCD compared to HBCD and SBCD. Signs of acute inflammation were mitigated within 2 h of film application in the cul-de-sac. Presence of sulphobutyl-ether β-cyclodextrin in the amlodipine-HPMC film can improve ocular permeation significantly and could be utilized as mucoadhesive type formulation for anti-inflammatory activity.

Bentonite clay based film formulation has been prepared for topical delivery of trimetazidine (TZ) for the control of ocular pressure. Trimetazidine ophthalmic film formulation has been prepared incorporating bentonite at 1: 0.0001 to 1: 0.00005 ratio in hydroxylpropyl methylcellulose (HPMC) matrix by solvent casting method. Film formulation showed controlled release of drug and thereby extending the ophthalmic permeation for more than 6 h. Permeation has been extended with the decrease of bentonite amount in the film. Sustained trimetazidine delivery has been characterized by the area under the decreased intraocular pressure (IOP) versus time curve after topical administered film formulation. In rabbits treated with film formulation TB3, the peak IOP dropped of almost 30% from the baseline at 240 min and persisted until 360 min and a good in vitro-in vivo correlation has also been established. The matrix formulation containing bentonite has shown higher negative biding energy values compared to the formulation without containing bentonite indicating stable interaction with improved bioavailability and sustained effect. Bentonite incorporated trimetazidine film formulation could be utilized in the control and management of intraocular pressure in rabbit.

In this investigation, the effect of kaolin on hydration kinetics and swelling behavior of hydroxypropyl methylcellulose ocular film was studied. Gradual reduction in the extent of and rate of swelling of the film was noticed with increasing the content of kaolin. Peppas model revealed that the diffusion coefficient was increased in the presence of kaolin and also increased for the film of higher viscosity polymeric film. Peppas model suggested that the polymeric film followed the diffusion-controlled swelling mechanism. The Peleg rate constant was increased from 1.69 to 44.39 h/g indicating the initial water adsorption rate in the decreasing order while Peleg capacity constant did not vary significantly in the presence and absence of kaolin indicating lack of remarkable change of water adsorption capacity. The presence of kaolin in the film could maintain a safe corneal hydration level.