Transcutaneous Delivery of Dexamethasone Sodium Phosphate Via Microneedle-Assisted Iontophoretic Enhancement - A Potential Therapeutic Option for Inflammatory Disorders.

AIM: This study aimed to fabricate dexamethasone sodium phosphate loaded microneedle arrays (MNA) and investigate their efficiency in combination with iontophoresis for the treatment of hind paw oedema in rats. METHODS: Drug loaded polyvinyl alcohol, polyvinyl pyrrolidone and D-sorbitol-based MNA11 were fabricated by vacuum micromolding. Physicochemical, morphological, thermal, in-silico, in-vitro insertion ability (on parafilm) and drug release studies were performed. Ex-vivo permeation, in-vivo insertion and anti-inflammatory studies were performed in combination with iontophoresis. RESULTS: MNA11 displayed sharp-tipped projections and acceptable physicochemical features. Differential scanning calorimetry results indicated that drug loaded MNA11 were amorphous solids. Drug interacted with PVP and PVA predominately via hydrogen bonding. Parafilm displayed conspicuously engraved complementary structure of MNA11. Within 60 min, 91.50 ± 3.1% drug released from MNA11. A significantly higher i.e., 95.06 ± 2.5% permeation of drug was observed rapidly (within 60 min) from MNA11-iontophoresis combination than MNA11 i.e., 84.07 ± 3.5% within 240 min. Rat skin treated using MNA11 and MNA11-iontophoresis showed disruptions / microchannels in the epidermis without any damage to underlying anatomical structures. MNA11-iontophoresis combination led to significant reduction (83.02 ± 3.9%) in paw oedema as compared to MNA11 alone (72.55 ± 4.1%). CONCLUSION: MNA11-iontophoresis combination can act as a promising candidate to deliver drugs transcutaneously for treating inflammatory diseases.

Preparation of Tamsulosin Hydrochloride-Loaded Mucoadhesive In Situ Gelling Polymeric Formulation for Nasal Delivery in Geriatrics.

This study aimed to prepare tamsulosin hydrochloride (HCl)-loaded in situ gelling formulation by using hydroxypropyl methylcellulose (HPMC), gellan gum, poloxamer 188, and benzalkonium chloride. Physicochemical evaluation of formulations included determination of pH, viscosity, gelation time, gel strength, drug content, and sterility. In silico study was performed to analyze interactions between polymers, drug, and mucin glycoprotein. In vitro degradation time, drug release, ex vivo mucoadhesion time, permeation, in vivo pharmacokinetics, and stability studies were performed to assess the formulation. Formulations were transparent and displayed acceptable physicochemical attributes. Tamsulosin HCl and polymers interacted via non-covalent interactions. HPMC formed hydrogen bonds, hydrophobic and van der Waals interactions with mucin protein while the drug formed hydrogen bonds only. Gel formulation degraded in simulated nasal fluid within 24 h. In situ gelling formulation showed 83.8 ± 1.7% drug release and remained adhered to the mucosa for 24.5 ± 1 h. A higher (~ 1.85 times) drug permeation was recorded through mucosa within 6 h by in situ gelling formulation when compared to control counterparts (aqueous solution of drug and in situ gelling formulation without poloxamer 188). Nasal administration of tamsulosin HCl by using in situ gelling formulation led to a ~ 3.3 and ~ 3.5 times, respectively, higher Cmax (maximum plasma concentration) and AUCtotal (total area under the curve) than the orally administered aqueous solution. Relative bioavailability of drug delivered by nasal in situ gelling formulation was 3.5 times the oral counterpart. These results indicated that the prepared in situ gelling formulation can act as a promising candidate for systemic administration of tamsulosin HCl.

Design and Evaluation of Hydrophobic Ion Paired Insulin Loaded Self Micro-Emulsifying Drug Delivery System for Oral Delivery.

Despite several novel and innovative approaches, clinical translation of oral insulin delivery into commercially viable treatment is still challenging due to its poor absorption and rapid degradation in GIT. Thus, an insulin-SDS hydrophobic ion pair loaded self-microemulsifying drug delivery system (SMEDDS) was formulated to exploit the hypoglycemic effects of orally delivered insulin. Insulin was initially hydrophobically ion paired with sodium dodecyl sulphate (SDS) to enhance its lipophilicity. The successful complexation of Insulin-SDS was confirmed by FTIR and surface morphology was evaluated using SEM. Stability of insulin after its release from HIP complex was evaluated using SDS PAGE. Subsequently, Ins-SDS loaded SMEDDS was optimized using two factorial designs. In vitro stability of insulin entrapped in optimized SMEDDS against proteolytic degradation was also assessed. Further, antidiabetic activity of optimized Ins-SDS loaded SMEDDS was evaluated in diabetic rats. Insulin complexed with SDS at 6:1 (SDS/insulin) molar ratio with almost five-fold increased lipophilicity. The SMEDDS was optimized at 10% Labraphil M2125 CS, 70% Cremophore EL, and 20% Transcutol HP with better proteolytic stability and oral antidiabetic activity. An Ins-SDS loaded SMEDDS was successfully optimized. Compared with insulin and Ins-SDS complex, the optimized SMEDDS displayed considerable resistance to GI enzymes. Thus, the SMEDDS showed potential for effective delivery of macromolecular drugs with improved oral bioavailability.

Improved Transdermal Delivery of Rabies Vaccine using Iontophoresis Coupled Microneedle Approach.

AIM: This study was aimed to develop rabies vaccine incorporated microneedle (MN) patches and evaluate the immunogenicity of prepared formulations in combination with iontophoresis. METHODS: Patches comprising of polyvinyl pyrrolidone, hyaluronic acid and polyethylene glycol 400 were engineered by vacuum micromolding technique. Physical evaluation of patches included determination of folding endurance, % swelling and morphological features. In vitro release study was performed in skin simulant agarose gel using model drug (methylene blue) loaded patches. In vitro insertion ability was assessed using stratum corneum simulant parafilm. In vivo insertion study was performed in rats. Immunogenicity was evaluated in dogs by determining immunoglobulin G (IgG) and rabies virus neutralizing antibodies (RVNA) titer. RESULTS: Patches displayed uniformly distributed microprojections with pointed tips and smooth surface, ~ 70% swelling, remained intact for ~ 200 foldings and successfully penetrated the parafilm. The area covered by model drug across agarose gel was almost double following treatment with MN-iontophoresis combination (MNdi) compared to MN alone (MNdo). Histological examination of rat skin treated with vaccine laden MN (MNvo) and MN-iontophoresis combination (MNvi) confirmed the formation of grooves in epidermis without any damage to the deep vasculature. A ~ 73% and ~ 206% increase (compared to untreated counterpart) was observed in the IgG titer of MNvo and MNvi treated dogs, respectively. The RVNA titer was increased by ~ 1.2 and ~ 2.2 times (compared to threshold value) after MNvo and MNvi treatment, respectively. CONCLUSION: MN-iontophoresis combination provided relatively potent immunogenic response over the conventional intramuscular injection, hence, can be used for administering vaccines transcutaneously.

Engineering of clarithromycin loaded stimulus responsive dissolving microneedle patches for the treatment of biofilms.

This study aimed to fabricate clarithromycin laden Eudragit S-100-based microfibers (MF), microfibers coated film (MB), clarithromycin loaded polyvinyl pyrollidone, hyaluronic acid and sorbitol-based dissolving microneedle patches (CP) and microfibers coated microneedle patches (MP). Morphological and phase analysis of formulations were carried out by scanning electron microscopy and differential scanning calorimetry, X-ray diffraction, respectively. Substrate liquefaction test, in vitro drug release, antimicrobial assay and in vivo antibiofilm studies were performed. MF exhibited a uniform surface and interconnected network. Morphological analysis of CP revealed sharp-tipped and uniform-surfaced microstructures. Clarithromycin was incorporated within MF and CP as amorphous solid. Liquefaction test indicated hyaluronate lyase enzyme responsiveness of hyaluronic acid. Fibers-based formulations (MF, MB and MP) provided an alkaline pH (7.4) responsive drug release; ∼79 %, ∼78 % and ∼81 %, respectively within 2 h. CP showed a drug release of ∼82 % within 2 h. MP showed ∼13 % larger inhibitory zone against Staphylococcus aureus (S. aureus) as compared to MB and CP. A relatively rapid eradication of S. aureus in infected wounds and subsequent skin regeneration was observed following MP application as compared to MB and CP indicating its usefulness for the management of microbial biofilms.

Fabrication and Characterization of Celecoxib-Loaded Chitosan/Guar Gum-Based Hydrogel Beads.

The aim of this study was to fabricate celecoxib-loaded chitosan/guar gum (CS/GG) single (SC) and dual (DC) crosslinked hydrogel beads using the ionotropic gelation approach. The prepared formulations were evaluated for entrapment efficiency (EE%), loading efficiency (LE%), particle size and swelling studies. The performance efficiency was assessed by in vitro drug release, ex-vivo mucoadhesion, permeability, ex-in vivo swelling and in vivo anti-inflammatory studies. The EE% was found to be ~55% and ~44% for SC5 and DC5 beads, respectively. The LE% was ~11% and ~7% for SC5 and DC5 beads, respectively. The beads showed a matrix-like network with thick fibers. The particle size of beads ranged from ~2.74 to 1.91 mm. About 74% and 24% celecoxib was released from SC and DC hydrogel beads, respectively, within 24 h. The SC formulation showed higher %swelling and permeability than the DC counterpart, while the %mucoadhesion was relatively higher for DC beads. During the in vivo study, a significant decrease in the inflammation of the rat paw and inflammatory markers including C-reactive proteins (CRP) and interleukin-6 (IL-6) was observed following treatment with the prepared hydrogel beads; however, the SC formulation showed better therapeutic efficiency. In conclusion, celecoxib-loaded crosslinked CS/GG hydrogel beads can provide sustained drug release and act as potential candidates for managing inflammatory conditions.

RP-HPLC based method for the determination of Tamsulosin HCl in API, Prepared dosage form and spiked plasma.

An analytical method for measurement of tamsulosin HCl from its different life cycle stages was developed using RP-HPLC technique. The elution of tamsulsoin was studied using MediterraneaTM Sea 18 column (dimesions 250 × 4.6 mm and pore size 5µm) and mobile phase comprising of buffer (pH 5.4): Acetonitrile (ACN) at ratio 60:40. The tamsolusin HCl elution was also studied by varying the operating conditions including the composition and flow rate of mobile phase, stationary phase temperature and scanning wavelength. The optimal elution conditions include; a) mobile phase flow rate; 1ml/min, b) wavelength; 224nm and stationary phase temperature 30°C. Linearity was recorded in the absorption data over tamsulosin concentration range of 0.007 to 40µg/ml. The values of paramters LOD and LOQ noted for tamsulosin dissolved in mobile phase were 0.0014 and 0.042µg/ml respectively, while for the counterpart in spiked plasma were 0.0017 and 0.051µg/ml respectively. The analytical method was prompt, accurate, reproducible and suitable for analysis of tamsulosin HCl in different samples of interest at formulation, regulation and clinical evaluations.