Prolonged Drug Delivery Research Articles

New and old drug delivery systems

SummaryEffective, prolonged and safe drug delivery to the eye in the treatment of ocular disease is a complex issue for clinical management. The approach to date has largely been adaptive: taking existing potent molecules which are active in reducing VEGF action and repurposing in new vehicles. From the point of view of a device, such materials may not be ideally druggable, the period of treatment too short or the true target involve more than one receptor. The dispersion of the dosage form is also an issue. Outside the eye, the drug may be lost by dilution and vascular/lymphatic clearance and inside, formulation debris at the back of the eye is a risk factor and may alter vision. The next generation of systems must address these concerns and utilize every tool at our disposal to improve efficacy. This includes the selection of better molecules, the use of modeling to better predict the disposition in the aged eye and perhaps the adoption of surgical procedures to increase drug flux more reliably. Up to now, we have relied on a singular approach – the drug‐ to solve the problem and now we realize that drug, vehicle and procedure must be integrated.

Microsphere: A Brief Review

Microspheres are multiparticulate drug delivery systems which are prepared to obtain prolonged or controlled drug delivery to improve bioavailability, stability and to target the drug to specific site at a predetermined rate. They are made from polymeric waxy or other protective materials such as natural, semi synthetic and synthetic polymers. Microspheres are characteristically free flowing powders having particle size ranging from 1-1000 μm consisting of proteins or synthetic polymers. The range of techniques for the preparation of microspheres provides multiple options to control as drug administration aspects and to enhance the therapeutic efficacy of a given the drug. These delivery systems offer numerous advantages compared to conventional dosage forms, which include improved efficacy, reduced toxicity, improved patient compliance and convenience. Such systems often use macromolecules as carriers for the drugs. The present review highlights various types of microspheres, different methods of preparation, its applications and also various parameters to evaluate their efficiency. Microspheres are various types like Bioadhesive microspheres, Magnetic microspheres, Floating microspheres, Radioactive microspheres, Polymeric microspheres, Biodegradable polymeric microspheres, Synthetic polymeric microspheres and are prepared by methods like Spray Drying, Solvent Evaporation, Single emulsion technique, Double emulsion technique, Phase separation coacervation technique, Spray drying and spray congealing, Solvent extraction, Quassi emulsion solvent diffusion. Microspheres have wide range of applications because of controlled and sustained release.

Direct fractionation of spray-dried polymeric microparticles by inertial impaction

The current study describes a convenient method for a direct size classification of spray-dried powders, which is of general interest for diverse applications in drug delivery. Accordingly, the time-consuming “trial-and-error” approach to identify critical formulation and process parameters influencing the final product specifications is replaced by a final fractionation step of the dried particles by inertial impaction.When employing the “original” vibrational spray-dryer (i.e., Nano Spray-Dryer B-90, Büchi) it was evident that both the liquid feed characteristics (e.g., concentration of dissolved solids) and process parameters (e.g., nozzle type and spray-rate) significantly affected the particle size and size distribution of generated sildenafil-loaded poly(lactide-co-glycolide) microparticles (particle size: ~4–~11μm; particle size distribution (span): ~1.3–~2.2). The said formulations showed prolonged in vitro drug release properties with mean dissolution times (MDTs) ranging between ~4 and ~14h. By contrast, replacing the electrostatic particle collector of the vibrational spray-dryer by a Next Generation Impactor enabled a direct size classification of spray-dried microparticles according to their aerodynamic behavior. Formulations collected from the individual impactor stages exhibited a defined particle size (i.e., stages I, II, III and IV with 7.8, 4.5, 3.0 and 2.1μm, respectively) and were significantly narrowly distributed (span: ≤1.2) than the non-fractionated controls. Likewise, fractionated formulations were characterized by a sustained sildenafil in vitro release behavior (MDT: ~1.5–~7h).Overall, regardless of the primary particle size and size distribution of spray-dried powders, desired size characteristics can be achieved by a terminal size classification by inertial impaction. Hence, the described approach provides spray-dried products meeting the specific requirements of the intended application (e.g., prolonged drug delivery to the lungs).

Bioabsorbable drug-eluting vascular scaffold for the treatment of coronary in-stent restenosis: A two center registry.

Coronary in-stent restenosis (ISR) is a clinical problem for which a satisfactory solution has not been found yet. Bioabsorbable drug eluting vascular scaffolds (BVSs) provide transient vessel scaffolding combined with prolonged drug delivery capability. The aim of this study was to investigate the safety of BVS for the treatment of coronary ISR. Between January 2013 and June 2013, 27 patients (31 lesions), presenting with either stable or unstable angina due to coronary ISR, were enrolled in a single arm, prospective, open label registry. Primary end point was the occurrence of target vessel revascularization (TVR) at 12 months. Secondary end point was the composite of death, myocardial infarction and TVR at 12 months. A diffuse ISR pattern was present in 70% of the lesions; mean lesion length was 34.6±15. BVS was successfully implanted in all patients with no in hospital MACE. At twelve months of follow up, MACE rate was 18.5%. One patient died for non-cardiac reason, one patient died due to a possible stent thrombosis and TVR was necessary in 3 patients (11.1%). Our data suggest that BVS is safe and technically feasible for treatment of long and diffuse coronary ISR. These data could be considered hypothesis generator for a randomized clinical trial.

Enhanced delivery of diclofenac diethylamine loaded Eudragit RL 100® transdermal system against inflammation

Abstract A transdermal therapeutic system (TTS) of diclofenac diethylamine (DDE) was developed to obtain a prolonged controlled drug delivery by the solvent evaporation technique. The matrix diffusion controlled systems used various combinations of hydrophilic (polyvinylpyrrolidone K30) and lipophilic (Eudragit RL 100® and Eudragit RS 100®) polymers containing dimethyl sulfoxide (DMSO) (0, 5 and 10% w/w) as a penetration enhancer. In vitro drug release was improved with an increased fraction of hydrophilic polymer. Formulation F8 containing Eudragit RL 100® and polyvinylpyrrolidone K30 in the ratio 40:60 presented the highest drug release (92.45%) and permeation rate (0.0988±0.010 mg/cm2/h) with sustained release action for 48 h. In vivo pharmacodynamic study of DDE-loaded Eudragit RL 100® transdermal system (formulation F8) showed significant higher percent inhibition of rat paw edema compared with the marketed formulation of the drug. Our results suggest that a developed formulation is an efficient system for transdermal diclofenac delivery against inflammation. The optimized formulation was found to be stable and did not show physicochemical interaction. The system is envisaged to be stable for a sufficiently long period (2.52 years) at room temperature.

A Review on Vaginal Drug Delivery System

Purpose: This review article has been written with a purpose to collate both conventional and novel vaginal drug delivery systems, highlighting the need and advantages of the novel vaginal drug delivery systems. This article will benefit the researchers working in the field of vaginal drug delivery with information about the current research being done in this area. Approach: The unique anatomy and physiology of the vagina is briefly described and then the various conventional and novel drug delivery systems such as vaginal films, vaginal rings, vaginal microspheres, vaginal liposomes, vaginal mucoadhesive caplets, vaginal mini tablets, and vaginal nanofibres are discussed. Research studies focusing on the novel vaginal drug delivery and their findings have also been reported. Findings: The novel vaginal drug delivery systems offer various advantages such as improved mucoadhesion, targeted drug delivery, prolonged drug delivery, improved stability and less frequency of dosing. Conclusion: Traditionally, intravaginal drug delivery has been restricted to delivery of anti infectives to the local vaginal cavity. With the rediscovery of the vaginal route as a potential route for the delivery of therapeutically important molecules, such as microbicides, novel vaginal drug delivery systems are being investigated. These novel systems would enhance the delivery of many drugs offering better therapeutic outcomes.

Formulation considerations in the design of topical, polymeric film-forming systems for sustained drug delivery to the skin

Polymeric film-forming systems (FFSs) are potential drug delivery systems for topical application to the skin. The FFSs form thin and transparent polymeric films in situ upon solvent evaporation. Their application convenience and cosmetic attributes, superior to conventional semi-solids, may offer improved patient compliance. This study represents the first phase of an investigation into the use of FFSs for prolonged dermal drug delivery. FFS formulations were distinguished based on their ability to sustain the release of betamethasone 17-valerate (BMV) in vitro over 72h. The effect of film-forming polymer (hydrophilic: hydroxypropyl cellulose (Klucel™ LF); hydrophobic: polymethacrylate copolymers (Eudragit® NE and Eudragit® RS), and polyacrylate copolymer (Dermacryl® 79) was first determined, and then the impact of incorporation of plasticisers (triethyl citrate, tributyl citrate, and dibutyl sebacate) was examined. The Klucel film released a significantly higher amount of BMV than the hydrophobic FFS, 42 versus 4μg/cm2, respectively. The release was increased when a plasticiser was incorporated, and with higher enhancement ratios achieved with the more lipophilic plasticisers. In conclusion, the results show that FFSs can sustain drug release (hence representing useful systems for prolonged dermal therapy) and emphasise the importance of the formulation on drug delivery, with the type of polymer being of greatest significance.

In-Situ Nasal Gel: A Review

Nasal therapy also called “Nasya Karma” has been recognized form of treatment in the Ayurvedic. System of Indian Medicine. Nowadays many drugs have better systemic bioavailability through nasal route as compared to oral administration. The nose is also considered an attractive route for needle-free vaccination and for systemic drug delivery, especially when rapid absorption and effect are desired. The nasal delivery is a feasible alternative to oral or parenteral administration for some drug because of the high permeability of the nasal epithelium, rapid drug absorption across this membrane and avidance of first pass metabolism. Prolonged drug delivery can be achieved by various new dosage forms like in-situ gel. In-situ forming polymeric formulation are drug delivery system that is in sol form before administration in the body, but once administered, undergoes gelation in-situ to form a gel. In-situ nasal drug delivery system is the type of mucoadhesive drug delivery system. Now a days insitu gel has been used as vehicle for the drug delivery of the drug for both local treatment and systemic effect. In-situ nasal gel drug delivery system is advantageous over the conventional drug delivery system like sustained and prolonged release of drug, reduced frequency of administration, improved patient compliance and comfort.

Hydrogels for ocular drug delivery and tissue engineering.

Hydrogels, as crosslinked polymeric three dimensional networks, possess unique structure and behavior in response to the internal and/or external stimuli. As a result, they offer great prospective applications in drug delivery, cell therapy and human tissue engineering. Here, we highlight the potential of hydrogels in prolonged intraocular drug delivery and ocular surface therapy using stem cells incorporated hydrogels.

Injectable scaffolds for bone regeneration.

Clinical treatments of significant bone defects involve invasive procedures such as the application of auto- and allografts. These procedures present many limitations including the potential for infection and rejection. There is therefore a need to develop novel therapeutic strategies able to exploit the natural regenerative potential of bone and that can be delivered in a less invasive manner. Among the materials studied for the development of novel scaffolds, stimuli-responsive gels containing hydroxyapatite and carbon nanotubes as nanofillers have generated great interest. In the present work, chitosan gels containing chitosan grafted CNTs and chitosan-hydroxyapatite complex have been formed by cross-linking with glycerol phosphate. The addition of the nanofillers afforded hydrogels with a faster sol/gel transition at 37 °C and enhanced mechanical properties. The thermosensitive composite gels also showed a good bioactivity profile associated with potential for the prolonged delivery of protein drugs. The inclusion of chemically cross-linked CNTs and HA in thermosensitive gels afforded injectable composite materials with enhanced properties, including reduction of gelation time, improved mechanical properties, good bioactivity, and prolonged drug release.

Aloin delivery on buccal mucosa: ex vivo studies and design of a new locoregional dosing system

Context: Chemoprevention of potential malignant disorders or cancerous lesions that affect oral mucosae requires extended duration of treatment. Locoregional delivery of natural products could represent a promising strategy for this purpose.Objective: To investigate the aptitude of aloin to permeate through, or accumulate in, the buccal mucosa and to develop a new prolonged oro-mucosal drug delivery system.Materials and methods: Permeation/accumulation of aloin from Curacao Aloe (containing 50% barbaloin) was evaluated ex vivo, using porcine buccal mucosa as the most useful model to simulate human epithelium. Oro-mucosal matrix tablets were prepared by dispersing aloin (10% w/w) in Eudragit® RS 100 as, biocompatible, low permeable, pH-independent, and non-swelling polymer. The prepared tablets were evaluated for drug–polymer compatibility, weight variation, drug uniformity content, diameter, thickness, hardness, friability, swelling, mucoadhesive strength, and drug release.Results: Aloin has low tendency to cross buccal mucosa, permeation is marginal, and high drug amounts remain entrapped into the epithelium. Matrix tablets characteristics were in agreement with pharmacopoeial requirements. Drug release showed highly reproducible Higuchian profile. Delivery through matrix tablets promoted drug accumulation in the mucosal tissue.Discussion and conclusion: Following application of matrix tablets on porcine buccal mucosa, the amount of discharged drug recovered in the tissue should be sufficient to produce the desired effects, providing therapeutic drug levels directly at the site of action. Aloin-loaded tablets are valid candidates for prevention/treatment of potentially malignant disorders and oral cancer and could potentially lead to clinically relevant drug delivery system as coadjuvant of conventional chemotherapy/radiation therapy.

Solid Lipid Nanoparticles and Nanostructured Lipid Carriers of Loratadine for Topical Application: Physicochemical Stability and Drug Penetration through Rat Skin

Purpose: To prepare solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) of loratadine (LRT) for the treatment of allergic skin reactions. Methods: SLN and NLC were prepared by high pressure homogenization method. Their entrapment efficiency (EE) and loading capacity (LC) were determined. The physical stability of nanoparticles was investigated during 6 months of storage at room temperature (RT), 4 and 40 o C. Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and laser diffraction (LD) were used for the investigation of drug:excipient compatibility, thermal behaviour and particle size of the nanoparticles. In vitro release and ex vivo skin penetration of LRT were studied. Nanoemulsions (NE) were also prepared and characterized for comparison. Results: Nanoparticles sizes ranged from 0.222 ± 0.011 μm to 0.252 ± 0.014 μm (D50 as a value based on the volume distribution, the maximum particle diameter below which 50 % of the sample volume exists) They were obtained with high drug payloads (> 90.67 %). LRT was compatible with the other excipients after 6 months. Particle size did not significantly alter particularly at RT. The highest release rate was obtained with NE (1.339 ± 0.026 mcg/ml/h) followed by NLC (1.007 ± 0.011 mcg/ml/h) and SLN (0.821 ± 0.012 mcg/ml/h), indicating anomalous transport (p 0.05). NE showed the highest penetration rate (0.829 ± 0.06 mcg/cm 2 /h) (p < 0.05). Conclusion: SLN and NLC of LRT are alternative formulations for immediate treatment of allergic skin reactions with prolonged drug delivery via reservoir action. Keywords : Loratadine, Transdermal delivery, Controlled drug delivery, Solid Lipid nanoparticles, Nanostructured lipid carriers, Allergy

In vitro and in vivo evaluation of thermosensitive chitosan hydrogel for sustained release of insulin

Injectable In situ gel-forming chitosan/β-glycerol phosphate (CS/β-Gp) solution can be introduced into the body in a minimally invasive manner prior to solidifying within the target tissue. This hydrogel is a good candidate for achieving a prolonged drug delivery system for insulin considering its high molecular weight. In addition to the physicochemical characterization of this hydrogel, in vitro and in vivo applications were studied as a sustained insulin delivery system. In the in vitro release studies, 19–63% of total insulin was released from the CS/β-Gp hydrogel within 150 h at different β-Gp and insulin concentrations. The best formulation was selected for in vivo experimentation to control the plasma glucose of diabetic mice models. The hypoglycemic effect of this formulation following subcutaneous injection in diabetic mice lasted 5 d, significantly longer than that of free insulin solution which lasted several hours.

A Polymerizable Bioionic Liquid Based Nanogel: A New Nanocarrier for an Anticancer Drug

Nanogels (NGs) are considered as one of the most suitable nanocarrier matrices for drug, gene and protein delivery. There are many methods of synthesis of NGs but polymerizable bioionic liquids are not being applied so far for the synthesis of such nanocarriers. The synthesis of a stimuli‐responsive NG system having average hydrodynamic size of 41 ± 15 nm is reported here, obtained by the simultaneous polymerization and crosslinking of a polymerizable biobased ionic liquid. The NG thus obtained shows prolonged drug delivery for 5‐fluorouracil, an anticancer drug, at pH 1.2 (stomach pH) for 10 days at physiological human body temperature (37 °C). However, no substantial drug delivery is observed at pH 5 and 7.4. Such a prolonged drug release profilemakes the reported NG system a potential candidate in the formulation of a pH‐sensitive drug nanocarrier vehicle for in vivo delivery of stomach‐specific therapeutic agents. image

Fibrin sealant as a carrier for sustained delivery of antibiotics

Objective: To evaluate the activity and sustained release of antibiotics from fibrin sealant against common strains of ocular bacteria. Methods: Vancomycin, ceftazidime, moxifloxacin and lomefloxacin were incorporated into fibrin sealant in the shape of discs. Each antibiotic disc and control fibrin disc without drug was tested in vitro against standard bacterial strains of Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae and Pseudomonas aeroginosa. After 24 hours of incubation at 37 °C, the discs were transferred to new plates of bacteria and triplicated for each antibiotic. Results: All antibiotic discs demonstrated detectable activity after 24 hours. Vancomycin had the longest duration of activity (4 days) on the S. pneumonia grown plate. The moxifloxacin discs showed a prolonged inhibition of S. aureus and S. pneumonia for 3 days and inhibited the other strains for 2 days. Conclusion: Fibrin sealants provided prolonged drug delivery, which indicates that antibiotic-loaded fibrin clots could be useful for early ocular postoperative care and treatment.

Chitosan/glucose 1-phosphate as new stable in situ forming depot system for controlled drug delivery

Chitosan (CS)-based thermosensitive solutions that turn into semi-solid hydrogels upon injection at body temperature have increasingly drawn attention over the last decades as an attractive new type of in situ forming depot (ISFD) drug delivery system. Despite the great potential of the standard CS/β-glycerophosphate (β-GP) thermogelling solutions, their lack of stability over time at room temperature as well as at refrigerated conditions renders them unsuitable as ready-to-use drug product. In the present study, we investigated Glucose-1-Phosphate (G1-P) as an alternative gelling agent for improving the stability of CS-based ISFD solutions. The in vitro release performance of CS/G1-P formulations was assessed using several model compounds. Furthermore, the local tolerance of subcutaneously implanted CS/G1-P hydrogels was investigated by histological examination over three weeks. The thermogelling potential of CS/G1-P solutions, determined by rheology, is dependent on the polymer molecular weight (Mw) and concentration as well as on the G1-P concentration. Differential scanning calorimetry (DSC) measurements confirmed that sol/gel transition takes place at around body temperature and is not fully thermo-reversible. The long term storage stability was evaluated through the appearance, pH, viscosity and gelation time at 37°C of the solution. The results emphasized an enhanced stability of the CS/G1-P system compared to the standard CS/β-GP. CS solution with 0.40mmol/g G1-P is stable for at least 9months at 2–8°C, versus less than 1month when using β-GP as gelling agent. Furthermore, the solution is easy to inject, as evidenced from injectability evaluation using 23–30G needles. In vitro release experiments showed a sustained release over days to weeks for hydrophilic model compounds, demonstrating thereby that CS/G1-P may be suitable for the prolonged delivery of drugs. The inflammatory reaction observed in the tissue surrounding the hydrogel in rats was a typical foreign body reaction, similar to the one observed for CS/β-GP hydrogels. These features confirm the potential of CS/G1-P solutions as an injectable ready-to-use in situ forming hydrogel.

Cationic core-shell nanoparticles for intravesical chemotherapy in tumor-induced rat model: safety and efficacy.

Mitomycin C (MMC) has shown potent efficacy against a wide spectrum of cancers and is clinical first choice in superficial bladder tumors. However, intravesical chemotherapy with MMC has been ineffective due to periodical discharge of the bladder and instability of this drug in acidic pH, both resulting in high rate of tumor recurrence and insufficiency to prevent progression. Nanocarriers may be a promising alternative for prolonged, effective and safe intravesical drug delivery due to their favorable size, surface properties and optimum interaction with mucosal layer of the bladder wall. Hence, the aim of this study was to evaluate and optimize cationic core-shell nanoparticles formulations (based on chitosan (CS) and poly-ϵ-caprolactone (PCL)) in terms of antitumor efficacy after intravesical administration in bladder tumor induced rat model. Antitumor efficacy was determined through the parameters of survival rate and nanoparticle penetration into the bladder tissue. Safety of the formulations were evaluated by histopathological evaluation of bladder tissue as well as observation of animals treated with MMC bound to nanoparticles. Results indicated that chitosan coated poly-ϵ-caprolactone (CS-PCL) nanoparticles presented the longest survival rate among all treatment groups as evaluated by Kaplan-Meier plotting. Histopathological evaluation revealed that cationic nanoparticles were localized and accumulated in the bladder tissue. As intravesical chemotherapy is a local therapy, no MMC was quantified in blood after intravesical instillation indicating no systemic uptake for the drug which could have subsequently led to side effects. In conclusion, core-shell type cationic nanoparticles may be effective tools for the intravesical chemotherapy of recurrent bladder tumors.

Drug Transport Mechanism of Oral Antidiabetic Nanomedicines

Context:Over the last few decades, extensive efforts have been made worldwide to develop nanomedicine delivery systems, especially via oral route for antidiabetic drugs. Absorption of insulin is hindered by epithelial cells of gastrointestinal tract, acidic gastric pH and digestive enzymes.Evidence Acquisition:Recent reports have identified and explained the beneficial role of several structural molecules like mucoadhesive polymers (polyacrylic acid, sodium alginate, chitosan) and other copolymers for the efficient transport and release of insulin to its receptors.Results:Insulin nanomedicines based on alginate-dextran sulfate core with a chitosan-polyethylene glycol-albumin shell reduced glycaemia in a dose dependent manner. Orally available exendin-4 formulations exerted their effects in a time dependent manner. Insulin nanoparticles formed by using alginate and dextran sulfate nucleating around calcium and binding to poloxamer, stabilized by chitosan, and subsequently coated with albumin showed a threefold increase of the hypoglycemic effect in comparison to free insulin in animal models. Solid lipid nanoparticles showed an enhancement of the bioavailability of repaglinide (RG) within optimized solid lipid nanoparticle formulations when compared with RG alone.Conclusions:Nanoparticles represent multiparticulate delivery systems designed to obtain prolonged or controlled drug delivery and to improve bioavailability as well as stability. Nanoparticles can also offer advantages like limiting fluctuations within therapeutic range, reducing side effects, protecting drugs from degradation, decreasing dosing frequency, and improving patient compliance and convenience

FORMULATION, OPTIMIZATION AND EVALUATION OF STOMACH SPECIFIC IN-SITU GEL OF HYDROCHLOROTHIAZIDE

The objectives of this research work were preparation, optimization and evaluation of in situ gelling system of Hydrochlorothiazide based on pectin that retains in the stomach by adherence to gastric wall provi ding an increased gastric residence time resulting in prolonged drug delivery in gastrointestinal tract. Pectin was used as a polymer and CaCO 3 as a cross - linking agent. The in situ formulation exhibited the expectations, viscosity, drug content and sustai ned drug release. This study reports that oral administration of aqueous solutions containing pectin results in formation of in situ gel and such formulations are homogenous liquids when administered orally and become gel at the contact site. The results o f a 3 2 full factorial design revealed that the concentrations of pectin and CaCO 3 significantly affected the dependent variables of viscosity, drug content (%) and Q 18 . These in situ gels are, thus, suitable for oral sustained release of Hydrochlorothiazid e . Key word: Hydrochlorothiazide, In - situ, polymer, Pectin, viscosity.

Modulation of the nano-tensile mechanical properties of co-blended amphiphilic alginate fibers as oradurable biomaterials for specialized biomedical application

The modulation of the mechanical properties of monolithic fibers by plasticizing and crosslinking enables the dynamic control of the nano-tensile forces, thereby obtaining optimized Young's modulus and ultimate strain for specialized application in the treatment of periodontal disease. In this work, drug-loaded crosslinked and plasticized alginate fibers (cl-PAFs) were prepared by extrusion-gelification with the aim of designing oradurable biomaterials for placement within the periodontal pocket and provide prolonged drug delivery. Mechanical properties of drug-free cl-PAFs were determined using a nanoTensile™ 5000 instrument and subsequently optimized versus the quantity of plasticizer and crosslinker as formulation variables employing a Box–Behnken experimental design strategy. Mechanically optimized fibers obtained (Young's Modulus=314.04MPa, yield stress=5.80MPa, ultimate strength=10.05MPa, ultimate strain=0.29MPa and toughness=2.39Jcm−3) were loaded with the model drugs ciprofloxacin and diclofenac both individually and simultaneously. The Young's modulus of cl-PAFs loaded with either drug individually exhibited a steep decline. However, in the case of cl-PAFs loaded with both drugs simultaneously, Young’s modulus regained the original value which may be attributed to the cohesive energy density, porosity and space filling. The effect of various formulation variables on the drug entrapment and release characteristics of the alginate fibers was elucidated at pH 4.0 and pH 6.8. Furthermore, a previously established atomistic computational model based on energy refinements was employed to mechanistically describe the fiber performance. The effect of varying the plasticizer and crosslinking ion concentration on Young’s modulus and ultimate strain of the linear elastic polymer matrix and the performance of the ciprofloxacin and/or diclofenac loaded optimized fiber was elucidated and conceptualized using molecular mechanics energy relationships (MMER) via the geometrical conformation and positioning of the molecular architectures.