Percentage Drug Release Research Articles

Preparation, Characterization and Optimization of Maltodextrin based Efavirenz loaded Proniosomes using Box Behnken Design: In vitro and ex-vivo permeation study

This research work focuses on development of proniosomal efavirenz (EFV) formulation using maltodextrin as a carrier. Thus an effort is made to increase the effectiveness of oral drug delivery of EFV by blending them in proniosomal powders (maltodextrin-based). The slurry method was employed for the preparation of proniosomes. A mix of Span-60, cholesterol and maltodextrin were used for its preparation..Box Behnken Design used to study the effect of independent variables X1, X2, and X3 (maltodextrin, Span-60 and cholesterol) on response variables Y1, Y2 and Y3 (Entrapment efficiency ,Vesicle size and Cumulative Drug Release percentage). Scanning Optical electron microscopy was used for studying surface-morphology of proniosome (optimized) and proniosome formation. To study any drug interaction or its conversion to the molecular and amorphous state from crystalline state, various tests like differential scanning calorimetry and FT-IR were performed. Compared to EFV in pure form, the proniosomalmaltodextrinbaseddrug showed better dissolution 98.41% in vitro-dissolution study. The optimized Efavirenz loaded proniosomal formulation showed maximum permeation (2614±215µg) in rat intestine as compared to pure drug(1500±114µg). The effectiveness of this drug (oral delivery) is obvious from the fact that rat intestine drug permeation is better. This shows maltodextrin-based EVF proniosomal formulation is suitable for oral delivery of efavirenz.

Doxorubicin-Loaded Multivesicular Liposomes (DepoFoam) as a Sustained Release Carrier Intended for Locoregional Delivery in Cancer Treatment: Development, Characterization, and Cytotoxicity Evaluation.

Despite the advantages of direct intratumoral (IT) injection, the relatively rapid withdrawal of most anti-cancer drugs from the tumor due to their small molecular size limits the effectiveness of this method of administration. To address these limitations, recently, increasing attention has been directed to using slow-release biodegradable delivery systems for IT injection. This study aimed to develop and characterize a doxorubicin-loaded DepoFoam system as an efficient controlled-release carrier to be employed for locoregional drug delivery in cancer treatment. Major formulation parameters, including the molar ratio of cholesterol to the main lipid [Chol/egg phosphatidylcholine (EPC)], triolein (TO) content, and lipid-to-drug molar ratio (L/D), were optimized using a two-level factorial design approach. The prepared batches were evaluated for encapsulation efficiency (EE) and percentage of drug release (DR) after 6 and 72 hours as dependent variables. The optimum formulation (named DepoDOX) was further evaluated in terms of particle size, morphology, zeta potential, stability, Fourier-transform infrared spectroscopy, in vitro cytotoxicity, and hemolysis. The analysis of factorial design indicated that TO content and L/D ratio had a negative effect on EE; between these two, TO content had the greatest effect. The TO content was also the most significant component, with a negative effect on the release rate. The ratio of Chol/EPC showed a dual effect on the DR rate. Using a higher percentage of Chol slowed down the initial release phase of the drug; nevertheless, it accelerated the DR rate in the later slow phase. DepoDOX were spherical and honeycomb-like structures (≈ 9.81 μm) with a desired sustained release profile, as DR lasted 11 days. Its biocompatibility was confirmed by the results of cytotoxicity and hemolysis assays. The in vitro characterization of optimized DepoFoam formulation demonstrated its suitability for direct locoregional delivery. DepoDOX, as a biocompatible lipid-based formulation, showed appropriate particle size, high capability for encapsulating doxorubicin, superior physical stability, and a markedly prolonged DR rate. Therefore, this formulation could be considered a promising candidate for locoregional drug delivery in cancer treatment.

Enhancing electroporation-induced liposomal drug release in suspension and solid phases

When exposed to an external electric field, lipid bilayer membranes are subject to increased permeability through the generation of pores. Combining this phenomenon, known as electroporation, with liposomal drug delivery offers the added benefit of on-demand release of the liposomal cargo. In previous studies, the maximum percent drug release when exposing liposomes to a pulsed electric field has not surpassed 30%, indicating most of the drug is still retained in the liposomes. Here we showed that by modulating the fluidity of the liposome membrane through appropriate selection of the primary lipid, as well as the addition of other fluidity modulating components such as cholesterol and biotinylated lipid, the electroporation-induced percent release could be increased to over 50%. In addition to improved induced release from liposomes in suspension, biomaterial scaffold-bound liposomes were developed. Electroporation-induced protein release from this solid phase was verified after performing further optimization of the liposome formulation to achieve increased stability at physiological temperatures. Collectively, this work advances the ability to achieve efficient electroporation-induced liposomal drug delivery, which has the potential to be used in concert with other clinical applications of electroporation, such as gene electrotransfer and irreversible electroporation (IRE), in order to synergistically increase treatment efficacy.

Preparation and physicochemical properties of cisplatin and doxorubicin encapsulated by niosome alginate nanocarrier for cancer therapy

Alginate (AL), in the form of a hydrogel, is extensively used in drug delivery. In the current study, an optimum formulation of alginate-coated niosome-based nanocarriers for co-delivery of doxorubicin (Dox) and cisplatin (Cis) was obtained for the treatment of breast and ovarian cancers in an attempt to decrease drug doses and overcome multidrug resistance. The physiochemical characteristics of uncoated niosomes containing Cis and Dox (Nio-Cis-Dox) compared to alginate-coated niosomes formulation (Nio-Cis-Dox-AL). The three-level Box-Behnken method was examined to optimize the particle size, polydispersity index, entrapment efficacy (%), and percent drug release of nanocarriers. Nio-Cis-Dox-AL showed appropriate encapsulation efficiencies of 65.54 ± 1.25 % and 80.65 ± 1.80 % for Cis and Dox, respectively. Maximum drug release decreased from niosomes in case coated by alginate. Also, the zeta potential value of Nio-Cis-Dox nanocarriers decreased after coating with alginate. In vitro cellular and molecular experiments were performed to investigate the anticancer activity of Nio-Cis-Dox and Nio-Cis-Dox-AL. MTT assay showed the IC50 of Nio-Cis-Dox-AL was much lower than the Nio-Cis-Dox formulations and free drugs. Cellular and molecular assays demonstrated that Nio-Cis-Dox-AL caused significant increase in apoptosis induction rate and cell cycle arrest in MCF-7 and A2780 cancer cells, as compared to Nio-Cis-Dox and free drugs. Also, the Caspase 3/7 activity increased after treatment with coated niosomes compared to uncoated nisomes and the drug-free case. Synergetic cell proliferation inhibitory impacts of Cis and Dox were demonstrated against MCF-7 and A2780 cancer cells. All anticancer experimental data demonstrated that the co-delivery of Cis and Dox through alginate-coated niosomal nanocarriers was effective for ovarian and breast cancer treatment.

Brain-targeted delivery of Valsartan using solid lipid nanoparticles labeled with Rhodamine B; a promising technique for mitigating the negative effects of stroke

The brain is a vital organ that is protected from the general circulation and is distinguished by the presence of a relatively impermeable blood brain barrier (BBB). Blood brain barrier prevents the entry of foreign molecules. The current research aims to transport valsartan (Val) across BBB utilizing solid lipid nanoparticles (SLNs) approach to mitigate the adverse effects of stroke. Using a 32-factorial design, we could investigate and optimize the effect of several variables in order to improve brain permeability of valsartan in a target-specific and sustained-release manner, which led to alleviation of ischemia-induced brain damage. The impact of each of the following independent variables was investigated: lipid concentration (% w/v), surfactant concentration (% w/v), and homogenization speed (RPM) on particle size, zeta potential (ZP), entrapment efficiency (EE) %, and cumulative drug release percentage (CDR) %. TEM images revealed a spherical form of the optimized nanoparticles, with particle size (215.76 ± 7.63 nm), PDI (0.311 ± 0.02), ZP (-15.26 ± 0.58 mV), EE (59.45 ± 0.88%), and CDR (87.59 ± 1.67%) for 72 hours. SLNs formulations showed sustained drug release, which could effectively reduce the dose frequency and improve patient compliance. DSC and X-ray emphasize that Val was encapsulated in the amorphous form. The in-vivo results revealed that the optimized formula successfully delivered Val to the brain through intranasal rout as compared to a pure Val solution and evidenced by the photon imaging and florescence intensity quantification. In a conclusion, the optimized SLN formula (F9) could be a promising therapy for delivering Val to brain, alleviating the negative consequences associated with stroke.

Study of Formulation and Process Variables for Optimization of Piroxicam Nanosuspension Using 32 Factorial Design to Improve Solubility and In Vitro Bioavailability.

Piroxicam is a Biopharmaceutical Classification System (BCS) Class II drug having poor aqueous solubility and a short half-life. The rationale behind the present research was to develop a Piroxicam nanosuspension to enhance the solubility and thereby the in vitro bioavailability of the drug. Piroxicam nanosuspension (PRX NS) was prepared by an anti-solvent precipitation technique and optimized using a full-factorial design. Herein, the nanosuspension was prepared using polymer polyvinylpyrrolidone (PVP) K30® and Poloxamer 188® as a stabilizer to improve the solubility and in vitro bioavailability of the drug. Nine formulations were prepared based on 32 full-factorial experimental designs to study the effect of the formulation variables such as concentration of poloxamer 188 (%) (X1) and stirring speed (rpm) (X2) as a process variable on the response of particle size (nm) and solubility (µg/mL). The prepared NS was characterized by phase solubility, Fourier-transform infrared (FT-IR), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), transmission electron microscopy (TEM), particle size, zeta potential, entrapment efficiency, and percent drug release. DSC and XRPD analysis of freeze-dried NS formulation showed conversion of PRX into a less crystalline form. NS formulations showed a reduction in the size from 443 nm to 228 nm with -22.5 to -30.5 mV zeta potential and % drug entrapment of 89.76 ± 0.76. TEM analysis confirmed the size reduction at the nano level. The solubility was increased from 44 μg/mL to 87 μg/mL by altering the independent variables. The solubility of PRX NS in water was augmented by 14- to 15-fold (87.28 μg/mL) than pure PRX (6.6 μg/mL). The optimized formulation (NS9) at drug-to-stabilizer concentration exhibited a greater drug release of approximately 96.07% after 120 min as compared to the other NS formulations and pure PRX (36.78%). Thus, all these results revealed that the prepared NS formulations have improved the solubility and in vitro dissolution compared to the pure drug. Furthermore, an increase in the drug release was observed from the NS than that of the pure PRX. All these outcomes signified that the prepared PRX NS showed an increase in solubility and in vitro dissolution behavior; which subsequently would aid in attainment of enhanced bioavailability.

Optimization of Nasal Liposome Formulation of Venlafaxine Hydrochloride using a Box-Behnken Experimental Design

Intranasal administration is among the most effective alternatives to deliver drugs directly to the brain and prevent first-pass metabolism. Venlafaxine-loaded liposomes are biocompatible carriers that enhance transport qualities over the nasal mucosa. This research aimed to develop, formulate, characterize, and observe the prepared formulation. The formulation was developed using the thin-film hydration technique. The response surface plot interrelationship between three independent variables are lipid, cholesterol and polymer and four dependent variables such as particle size, percentage entrapment efficiency, and percentage drug release were ascertained using the Box-Behnken design. The drug-release chitosan-coated liposomes were reported to have a particle size distribution, entanglement efficiency, and 84%, respectively, of 191 ± 34.71 nm, 94 ± 2.71% and 94 ± 2.71%. According to in vitro investigations, liposomes as a delivery system for the nasal route provided a more sustained drug release than the oral dosing form. The intranasal administration of venlafaxine liposomal vesicles effectively enhanced the absolute bioavailability, retention time, and brain delivery of venlafaxine.

Fabrication and characterization of Orlistat Liquisolid tablets

The aim of the work was to improve the dissolution properties of the practically insoluble anti-obesity drug, Orlistat by utilizing liquisolid technique. Different liquisolid tablets were prepared by dissolving Orlistat in PG with Avicel PH 102 as carrier, Aerosol 200 as coating material and Sodium starch glycolate as disintegrating agent. Additives such as PVP, HPMC and HPG were incorporated into the formulations to improve dissolution characteristics. The formulated liquisolid tablets were evaluated for post compression parameters such as weight variation, hardness, friability, drug content and in-vitro dissolution studies. FT-IR study suggested that there was no chemical interaction between the drug and excipients. DSC was performed to evaluate the physicochemical properties of the liquisolid tablets, which confirm the conversion of crystalline form of the drug to the amorphous form in liquisolid tablets. The result showed that liquisolid formulation of Orlistat exhibited higher percentage of drug release than directly compressed tablets which show significant benefit of liquisolid tablet in increasing wetting properties and surface area of drug available for dissolution.

High drug-loading and controlled-release hydroxyphenyl-polyacrylate adhesive for transdermal patch.

Long-acting transdermal drug delivery system (TDDS) requires high drug-loading and drug controlled-release. To simultaneously improve drug-polymer miscibility and realize drug controlled-release, this work aimed to develop a new pressure sensitive adhesive modified with hydroxyphenyl (HP-PSA) by introducing doubly ionic H-bond into drug-PSA interaction. Eight model drugs divided into R3N, R2NH and no N type were chosen to understand the characteristics of the HP-PSA and inner mechanism. The results showed that the doubly ionic H-bond between R3N and R2NH type drugs and HP-PSA, differing from the ionic bond and neutral H-bond, was a reversible and relatively strong interaction. It could significantly enhance their drug-loading by 1.5 to 7 times and control drug release rate to its 1/5 to 1/2 without altering its total release properties, outperforming the commercial Duro-Tak® 87-2510 and Duro-Tak® 87-2852 adhesives. According to the pharmacokinetics results, the high drug-loading patches based on HP-PSA achieved a sustainable plasma drug concentration avoiding burst release, and over 2 times area under concentration-time curve (AUC) as well as 6 times mean residence time (MRT) revealed its potential to realize long-acting drug delivery. Additionally, its safety and mechanical features were satisfied. The mechanism study showed that the repulsion of the ionic drugs in HP-PSA increased drug-loading, and the relatively strong interaction could also control drug release. The incomplete H-bond transfer determined its reversibility, thus making the drug release percentage up to that of non-functional PSA. In conclusion, the high drug-loading efficiency and drug controlled-release capacity of HP-PSA, as well as its unique interaction, would contribute to the development of TDDS. Moreover, the construction of the doubly ionic H-bond would provide further inspiration for various drug delivery systems in the non-polar environment.

Formulation and evaluation of sustained releasedomperidone hydrochloride transdermal patches to treat motion sickness

Objective: Transdermal route of drug delivery is superior than oral route because it avoids first pass effect, ensures better patient compliance, reduce dosing frequency especially in extended-release formulation and is easy to use. Domperidone HCl is DA2 receptor antagonistic and is used to prevent nausea and vomiting. The objective was to formulate a domperidone HCl extended-release transdermal drug delivery system to treat motion sickness. Methods: Five different formulations were formed using different solvents (methanol and dichloromethane) and polymers (HPMC and Eudragitl-100) by solvent evaporation method. 500mg of domperidone HCl was added in each patch and dibutyl phthalate was added as plasticizer. A 3% w/v PVA layer was used as backing. All these formulations were evaluated for their physicochemical properties (weight variation, thickness, folding endurance and tensile strength), in-vitro drug release, drug contents determination, any incompatibility between drug and excipients by FTIR and DSC and skin irritation. Results: All formulations exhibited good physicochemical properties and percentage drug release during 24 hours was 79.3%, 97.1%, 96.8%, 74.7% and 59.7% respectively. F-YM showed maximum in-vitro drug release. The optimized formulation (F-YM) followed Korsmeyer Peppas release model with n=0.383 showing that the system was following dissolution dependent drug release. No interaction between drug and excipients was detected by DSC and FTIR. No skin irritation was detected. Conclusion: The extended release transdermal patches of domperidone HCl to treat motion sickness were prepared and formulation F-YM showed optimized behavior with maximum in vitro drug release.

Synergistic effect of polymer functionalized graphene oxide system for breast cancer treatment

The multifaceted drug carrier system is an emerging trend in delivering chemotherapeutic drugs and photosensitizers for the synergistic effect. In this work, we have designed a functionalized graphene oxide (GO) based carrier system for combined chemo-photodynamic therapeutic effects. Doxorubicin (DOX) and rose bengal (RB) were entrapped on the surface of GO via hydrophobic and π-π stacking interactions. The functional group determination, crystalline properties, surface morphology, and hydrodynamic size were evaluated using FT-IR, XRD, SEM, TEM, AFM, and DLS analysis. At 24 h, the entrapment efficiency was 65 % DOX and 40.92 % RB, and the loading capacities were 16.9 % DOX and 5.68 % RB observed at 30 min. The drug release percentage was higher in pH-2.6 rather than in pH-5.5, 6.8, and 7.4 pH environments. The in-vitro toxicity analysis using the LDH assay reveals that the DOX and RB co-loaded carriers had a significant cytotoxic effect on MCF-7 cells, indicating that the carrier could improve the therapeutic efficacy of DOX. Morphological changes were studied using inverted light microscopy; the cells were irradiated with a laser 525 nm 10 J/cm2 for 2 min 51 sec, and it was observed that the DOX and RB co-loaded carrier with laser-irradiated cells exposed the high-level morphological changes with the occurrence of apoptotic cell death. Compared to free DOX, the DOX/RB co-loaded carrier + laser had an efficient anticancer activity, as confirmed by DAPI staining cell uptake, flow cytometry, and intracellular ROS generation analysis. The DOX and RB co-loaded carrier clearly exhibits the RB-mediated photodynamic action on MCF-7 cells in response to external laser light irradiation. It permits an on-demand dual-payload release to trigger an instantaneous photodynamic and chemo treatment for cancer cell eradication. Finally, the ensuing dual-agent release is probable to successfully fight cancer via a synergistic effect.

Physicochemical and In-Vitro Equivalence of 15 Generic Amlodipine Besylate Tablets Marketed in Davao City, Philippines

This study investigated the physicochemical and in-vitro equivalence of the innovator and fifteen generic brands of amlodipine besylate tablets marketed in selected community drugstores in Davao City, Philippines. The samples were coded from A to P and assayed for weight uniformity, hardness, friability, disintegration, potency, content uniformity, and dissolution using the methods described in the USP. The percentage of drug content was determined using the spectrophotometric method. The results showed that all brands conformed to the USP standard for weight uniformity, friability, and disintegration test. In addition, nine generic brands did not conform to the USP standard for the hardness test. All brands meet the USP requirement for potency with a mean content of not less than 90% and not greater than 110% of the labeled claim. Six generic brands did not conform to the USP standard for content uniformity, with acceptance values higher than the specification of 15.0%. All brands conformed to the USP standard for dissolution or percentage drug release. Further, the dissolution profile comparisons showed that 14 out of 15(93.33%) generic brands of amlodipine besylate tablets could be used interchangeably with the innovator drug. In conclusion, this study confirmed the importance of continuous monitoring of generic drugs' safety, quality, and efficacy to ensure equivalence and compliance with pharmacopeia standards and aid the prescribers’ decision-making in generic dispensing.

Fabrication, Optimization and Characterization of Floating Microspheres of Quinapril Hydrochloride using Factorial Design Method

The majority of formulations are available as oral dosage forms. In spite of some pharmaceutical challenges, this route is considered as most suitable way of drug delivery. For that reason it is necessary to optimize dose and dosing frequency to reduce the toxic effects of drug. Therefore, in this study, we have conceptualized the fabrication of floating microspheres of Quinapril Hydrochloride by the solvent evaporation technique with varying ratios of HPMC, Carrageenan, and Poly methyl methacrylate with polyvinyl alcohol that will augment its gastric retention time in conjunction with the sustained pharmacological activity. The formulation process of floating microspheres was optimized for stirring speed (X1) and concentration of polymer ratio (X2) on dependent variables such as percentage entrapment efficiency (Y1), percentage yield (Y2), in vitro buoyancy (Y3), and percentage of drug release (Y4) by using the factorial design. The drug was characterized by Fourier transform infrared spectroscopy, Differential scanning calorimetry was used for the identification of drug polymer blend interaction. The prepared microspheres were characterized by number of parameters including; scanning electron microscopy, percentage yield, particle size, in vitro buoyancy, drug entrapment efficiency, in vitro drug release, and in vivo floating behavior in albino rabbits. The release profile of microspheres prepared with hydrophilic, pore forming material and ion exchange resin combinations was dependent on the layer of pores developed by the fluid present at the absorption site of stomach and the drug release rate was retarded at site of action i.e. GIT.

Development, Optimization and Evaluation of Herbal Patch Formulation for Acne Treatment

Background: More than 85% of young people around the world suffer from acne vulgaris, which is the most prevalent chronic inflammatory skin illness. The study’s objective was to develop a herbal patch formulation contained quercetin, curcuminoids, and berberine HCl for the treatment of acne that utilizing ethyl cellulose and HPMC K4M as polymers and propylene glycol as a plasticizer. Materials and Methods: Drug excipient compatibility study was performed using FT-IR. Preliminary trial was done for screening of polymers and plasticizer concentrations. The combined influence of the two independent variables, namely the concentration of HPMC K4M and ethyl cellulose, on the dependent variables, tensile strength and cumulative % drug release at 24 hr, was examined using a 32 full factorial design. Patches were evaluated for physicochemical parameters. Results: Drug excipient compatibility study revealed that drug and excipients are compatible with each other. The optimized formulation (C0) showed tensile strength 2.56 kg/cm2, cumulative percentage drug release of quercetin, berberine HCl, and curcuminoids at 24 hr were 94.02%, 64.66%, and 94.21%, respectively. Tensile strength increased with an amount of HPMC K4M and Ethyl cellulose increases, the cumulative percentage of drug release decreased as HPMC K4M and ethyl cellulose concentrations were raised. Conclusion: Optimized herbal patch formulation had shown good physico-chemical and mechanical properties. The research shows that the developed formulation has the potential to be a useful replacement for the present medications in the market.

Polymeric Nanocarrier system Bearing Anticancer Agent for the Treatment of Prostate Cancer: Systematic Development and in vitro Characterization

Objectives: Doxorubicin-bearing polymeric (PLGA) nanoparticles (PNPs) were prepared for the treatment of prostate cancer. Materials and Methods: These PNPs were prepared using the solvent evaporation method and characterized using UV, NMR, Particle size Analyser, SEM, and TEM for the determination of shape, size, zeta potential, and polydispersity index. Moreover, in vitro drug release, SRB assay, apoptosis, and haemolytic study were also performed to prove its potentiality for prostate cancer. Results: The mean particle size (MPS), polydispersity index (PDI), and zeta potential (ZP) of PNPs were found to be 101.3 ± 1.23 nm, 0.240 ± 0.28 and -3.11 ± 1.96 mV, respectively. SEM and TEM revealed that the PNPs are spherical in shape and the sizes are approximately 100 nm. The entrapment efficiency, loading efficiency, and percentage drug release of doxorubicin from PNPs were found to be 69.38 ± 1.76%, 4.2 ± 0.64% and 77.56 ± 4.24%, respectively. In addition, cellular apoptosis against PC-3 cell lines was found to be ≥ 5.15 fold and haemolysis toxicity was reduced to ≤ 3.5 fold with PNPs as compared to free drug. Conclusion: These findings demonstrated that PNPs have the potential to deliver the anticancer agent to tumor sites and could be an emerging strategy for the treatment of prostate cancer.

Formulation Development of Flaxseed Oil Beads Containing ω-Fatty Acid

Background: Nutraceuticals are in high demand as dietary supplements on the international market since decades. Nutritional and therapeutic supplements called nutraceuticals are widely accessible. Alpha linolenic acid (ALA), fibre, proteins, and vital omega-3 fatty acids are all present in high concentrations in flaxseed, one of the oldest and most widely utilised food supplements. The present work was aimed to formulate and develop flaxseed oil beads containing omega fatty acids as a replacement supplement for marine source. Flaxseed oil beads were formulated by ionic gelation method. Minitab 21.1.0 was used to screen and optimise the process and formulation parameters. Plackett Burman design was used for the initial screening. Twelve batches were made ready for screening, and each batch was evaluated for optimization based on the percentage of drug release and the percentage of drug encapsulation efficiency. RSM was used to carry out the optimization. After optimization and validation, the batches showed the satisfactory results complying with IP specifications.
 Results: Twelve batches were formulated and evaluated for percentage encapsulation efficiency and percentage drug release. The formulated batches F4, F6 and F10 shown the optimal results.
 Conclusion: Polyunsaturated fatty acids found in the flaxseed oil were confirmed with hexabromide test. Several nutritional advantages of the extracted flaxseed oil's omega fatty acid were incorporated in beads utilising the ionic gelation process.
 Keywords: Nutraceutical, Flaxseed, Beads, QbD, Omega fatty acid, Alpha linolenic acid.

Preparation and optimization of colon-targeted Pectin-Chitosan microsphere containing Diloxanide furoate-hydroxypropyl-β-cyclodextrin inclusion complex for effective treatment of amoebiasis

Degradation in the upper gastrointestinal tract increases the unwanted dose of Diloxanide furoate.(DF) as an anti-amoebic drug, the use of colonic delivery of it is a promising approach to reduce its dose and dose-dependent side effects. An investigation was done to prepare and evaluate the microsphere for site-specific delivery using surface response curve methodology to optimize independent variables like concentration of polymer (Pectin and Chitosan), crosslinking agent, and time of hardening and the dependent variable like percentage drug entrapment and drug release in an acidic environment. The microsphere was prepared by dropping of optimized inclusion complex of DF and hydroxypropyl-β-cyclodextrin with anionic polymer (Pectin) to a solution of cationic polymer containing different concentrations of calcium chloride. Prepared microspheres were characterized by swelling behavior, In vitro release in various simulated gastric and intestine fluids. The results suggest that pectin 6%, Chitosan 3.5%, CaCl2 6%, and cross-linking time 20 min shows a promising approach to colonic delivery of DF for not only better retreatment of amoebiasis but also for reducing dose-related side effects.

Development of 3D-printed subcutaneous implants using concentrated polymer/drug solutions

Implantable drug-eluting devices that provide therapeutic cover over an extended period of time following a single administration have potential to improve the treatment of chronic conditions. These devices eliminate the requirement for regular and frequent drug administration, thus reducing the pill burden experienced by patients. Furthermore, the use of modern technologies, such as 3D printing, during implant development and manufacture renders this approach well-suited for the production of highly tuneable devices that can deliver treatment regimens which are personalised for the individual. The objective of this work was to formulate subcutaneous implants loaded with a model hydrophobic compound, olanzapine (OLZ) using robocasting - a 3D-printing technique. The formulated cylindrical implants were prepared from blends composed of OLZ mixed with either poly(caprolactone) (PCL) or a combination of PCL and poly(ethylene)glycol (PEG). Implants were characterised using scanning electron microscopy (SEM), thermal analysis, infrared spectroscopy, and X-ray diffraction and the crystallinity of OLZ in the formulated devices was confirmed. In vitro release studies demonstrated that all the formulations were capable of maintaining sustained drug release over a period of 200 days, with the maximum percentage drug release observed to be c.a. 60 % in the same period.

Formulation Development and Evaluation of Once Daily Fexofenadine Hydrochloride Microsponge Tablets

The objective of present study was to formulate and develop once daily Fexofenadine Hydrochloride tablets to improve the aqueous solubility by microsponge technology. Fexofenadine Hydrochloride is an antihistamine and belongs to BCS class-III with low permeability and poor bioavailability about 30 - 35 %. The microsponges were prepared by Quashi emulsion solvent diffusion method with Quality by design approach. The study of effect of independent variables Eudragit EPO (500 to 1,000 mg), internal phase volume (DM: ETH) (5 to 10 mL) and RPM (500 to 1,000) on responses were analyzed to optimize the formulation with desirable results by using central composite design and response surface method. Optimized formulation F22 showed percent production yield (99.10 %), percent drug entrapment (99.45 %), particle size (94.12 µm) and percent drug release of prepared tablets at 5, 10, 15 and 30 min were 60.6, 80.75, 87.47 and 92.85 %, respectively. It showed Higuchi mechanism of release kinetics by diffusion. In vivo pharmacokinetics of the prepared tablets was studied in rabbits (IAEC/NRML/2022–2023/09) with and without permeation enhancer to find the rate of absorption. when compared to Marketed product -Allegra 24 (F21) with (t1/2 absorption) 0.192711±0.00278 h and MRT 19.10608±0.257571 h and formulation without poloxamer 407 (F22) (t1/2 absorption) 0.165013±0.024164 h and MRT 19.32228±0.764531 h, maximum absorption was observed for the Formulation F23 with poloxamer 407 (15 %) with (t1/2 absorption) of 0.144662±0.006787 h and Mean residence time (MRT) of 24.10796±1.01232 h. Microsponge technique improved the aqueous solubility of the fexofenadine Hydrochloride and Eudragit EPO extended the mean residence time up to 24 h along with improved permeability in presence of Poloxamer 407 to full fill the needs of BCS class-III drug. HIGHLIGHTS Fexofenadine Hydrochloride has poor aqueous solubility and low passive permeability P-Glycoprotein efflux induced intestinal secretion is the reason for the incomplete absorption (35 %) following oral absorption There is a need to increase bioavailability and maintenance of steady state plasma concentration Microsponge drug delivery systems improvise the solubility of drug due to its porous nature Microsponge drug delivery system can fulfill the requirements by increasing the permeability and modifying the drug release from dosage form GRAPHICAL ABSTRACT

Synergistic effect of cerium and structure directing agent on drug release behavior and kinetics

This work was mainly aimed at the study of the dual effect of cerium and structure directing agent template concentration, on vancomycin release profiles and kinetics from Ce-substituted mesoporous bioactive glasses (MBGs). MBG based on (20-x) B2O3 - 55 SiO2 – 20 CaO – 5 P2O5 – x Ce2O (x = 0, 1 and 3 mol %) was synthesized by the evaporation-induced self-assembly process using two molar ratios (0.01 and 0.02 molar ratio) of nonionic block copolymer Pluronic® 123 (P123) surfactant. The TGA-DTA, FTIR, and textural features analyses were carried out for the glasses. Moreover, the in vitro bone-forming activity and degradation analysis were tested using simulated body fluid (SBF). The drug loading capacity, drug release profile, and kinetics (using different kinetic models such as first order, Higuchi, Hixson-Crowell, and Baker-Lonsdale models) were determined using vancomycin as a drug model. The results showed that the isotherms of all MBGs fit with type IV isotherms, and the surface area of MBGs synthesized by 0.02 M template was higher than that prepared by 0.01 M, where it ranged from 174.05 m2.g−1 to 256.73 m2.g−1. The pore size diameter was decreased as cerium content increased in all MBGs (decreased from 5.44 to 3.54 nm). Moreover, the MBGs induced the formation of a bone-like apatite layer, and their biodegradation properties can be tailored by controlling glass composition. Furthermore, Ce-free MBGs showed the lowest drug adsorption and the highest drug release percentage. The drug release kinetic was best fitted with Higuchi and Baker-Lonsdale models which denoted that the mechanism of drug release from MBGs was a diffusion release from spherical particles. In conclusion, vancomycin release was controlled by the glass composition. Meanwhile, the MBGs synthesized in this study are proposed to be applied for bone regeneration, bone cancer treatment, and reducing the bacterial activity around the tumor site.Graphical abstract