Drug Delivery Letters - Volume 11, Issue 1, 2021

Bioadhesive films are considered a novel drug delivery system thatprovides improved therapy and better patient compliance than conventional dosage forms. The type and concentration of polymer or the blend of polymers used are important factors that can influence the properties of bioadhesive films, the product outcome and the performance. But the modification of available polymers to synthesize polymers with improved properties is the current area of research. Furthermore, addressing the challenges in formulating bioadhesive films for transdermal delivery of a variety of different classes of drug molecules is the frontier for future research. With the advancement of synthetic chemistry and the development of newer technology like 3D printing, more studies are being conducted on bioadhesive films that have opened up many opportunities in this field of research. This article reviews the current advancements in developing bio-adhesive films and provides basic principles that will be helpful to overcome the difficulties that are associated with the design of formulation.

Background: Metronidazole (MTZ) is an anti-oxidant and anti-inflammatory agent with beneficial therapeutic properties. The hydrophilic nature of the molecule limits its penetration across the skin. Existing commercial formulations have limitations of inadequate drug concentration present at the target site, which requires frequent administration and poor patient compliance. Objective: The aim of the current study was to develop and evaluate water in oil microemulsion of Metronidazole with higher skin retention for the treatment of inflammatory skin disorders. Methods: Pseudo ternary phase diagrams were used in order to select the appropriate ratio of surfactant and co-surfactant and identify the microemulsion area. The selected formulation consisted of Capmul MCM as oil, Tween 20 and Span 20 as surfactant and co-surfactant, respectively, and water. The formulation was characterized and evaluated for stability, Ex vivo permeation studies and in vivo anti-inflammatory effect (carrageenan induced rat paw edema, air pouch model), anti-psoriatic activity (mouse-tail test). Results: The particle size analyses revealed the average diameter and polydispersity index of the selected formulation to be 16 nm and 0.373, respectively. The results of ex vivo permeation studies showed statistically higher mean cumulative amount of MTZ retained in rat skin from microemulsion, i.e., 21.90 ± 1.92 μg/cm², which was 6.65 times higher as compared to Marketed gel (Metrogyl gel®) with 3.29 ± 0.11 μg/cm² (p<0.05). The results of in vivo studies suggested the microemulsion based formulation of MTZ to be similar in efficacy to Metrogyl gel®. Conclusion: Research suggests the efficacy of the developed MTZ loaded microemulsion in the treatment of chronic skin inflammatory disorders.

Objective: The goal of this research was to optimize and evaluate an intrapocket dental film, composed of polycaprolactone and carbopol blends for the management of periodontitis. Methods: The intrapocket dental film was prepared using a modified solvent casting method, followed by characterization, in-vitro release, in-vitro antimicrobial activity, and in-vivo efficacy on the periodontitis animal model. Result: Prepared films were consistent in thickness (2.10±0.56 to 2.50±0.39 mm) and weight (35.23±0.37 to 39.45±0.45 mg) with drug entrapment of up to 87.63±1.98 percent. The concentration of carbopol is observed to have a direct relationship with the thickness, film weight, and swelling factor of the prepared dental film. The film has a surface pH close to gingival crevicular fluid pH and is therefore appropriate for the application. The developed film exhibited a biphasic drug release profile with an initial burst release followed by a continuous release for more than 11 days. Drug release kinetic study supports the release of the drug by a diffusion-based process, as best explained by the Korsmeyer Peppas kinetics (R² =0.9635). in vitro antimicrobial activity was also in accordance with drug release, with a high initial zone of inhibition (ZOI) (49.32±0.156mm), followed by 14.28±0.080 mm ZOI on the 11^th day. The in vivo study showed that the prepared film was able to prevent periodontal ligament degeneration, as observed in the periodontitis experiment animal model. Conclusion: The prepared intrapocket dental film based on caprolactone and carbopol can be used as a novel local drug delivery system for the management of periodontitis.

Background: The chronotherapy concept attains considerable focus towards itself due to its pulsatile fashion rather than continuous delivery. The delivery of the right amount of drug to the target organ at the most appropriate time is fulfilled by using the chronotherapeutic dosage form. Aim: The present study aims to develop and evaluate a chronotherapeutic drug delivery system by using natural polymer for time-specific drug delivery at the target site. Methods: Tamarind seed polysaccharide was extracted and used in the preparation of core tablets. Nine formulations of core tablets were prepared with nifedipine at 5 tonnes of pressure on a 6 mm punch. The core tablets were prepared by using the compression coating method. The three batches F1, F2, and F3 were prepared by using tamarind gum in different concentrations i.e., 45%, 22.5%,and 67.5%, respectively, and compressed at 8 tonnes of pressure on 12 mm of punch. The finally compressed tablet was coated with different concentrations of ethyl cellulose in which isopropyl alcohol was used as a solvent. In a controlled medium, a stability study was performed to evaluate the physical appearance, drug content, and release of the prepared core tablet. Result and Discussion: All the nine formulations of tablets were prepared successfully and the evaluation studies (thickness, weight variation, hardness, friability, etc.) revealed that all the formulations were within the official range. The release study of the drug revealed that the formulation F7 containing 67.5% of tamarind polymer, coated with 2%, 4%, and 5% of ethylcellulose solution released 59.68 ± 1.03% (Q50%) drug within 5 h whereas 87.09 ± 2.08% (Q80%) within 6 h and 97.74 ± 2.19% of the drug was released within 12 h. The formulation F7 was found to be more effective as it released the maximum amount of drug in a short period as compared to other formulations. Conclusion: The coating of core tablets allowed to prepare pharmaceutical dosage form for timespecific drug delivery. These chronotherapeutic core tablets can be used for the treatment of angina pectoris and hypertension, etc.

Aim: Due to the various drawbacks associated with current treatment therapy of onychomycosis, the main aim was to develop thermosensitive hydrogels and thermosensitive polypseudorotaxanes hydrogels-based nail lacquer for transungual delivery of Efinaconazole for the management of onychomycosis. The objective is to enhance the permeation and retention of the drug in the nails and improve patient compliance. Methods: Poloxamer 407 and Hydroxy Propyl-β-cyclodextrin were used to prepare the nail lacquers. 2-mercaptoethanol was added as a penetration enhancer to improve the penetration of the drug across the nail plate. The formulations were optimized by varying the concentration of poloxamer and water: ethanol ratio and evaluated based on the basis of drying time, sol-gel transition temperature, ex vivo drug release, and viscosity. The optimized formulation was further evaluated for pH, water resistance, non-volatile content, drug content, blush test, spreadability, and stability studies. Results: The increase in ethanol concentration and reduction in poloxamer proportion led to a reduction in lacquer stickiness thus, improving the lacquer drying time and penetration. The polypseudorotaxanes improved the permeation profile of the drug in comparison to the marketed nail lacquer. The presence of 2-mercaptoethanol also contributed to the transungual delivery of Efinaconazole. Conclusion: The polypseudorotaxanes based nail lacquer with the incorporation of penetration enhancer was able to achieve a high rate of drug penetration and retention, thus supporting the potential use of aqueous based-nail lacquer in transungual drug delivery for the onychomycosis treatment.

Background: Knowledge of the permeation characteristics of new chemical entities across biological membranes is essential to drug research and development. Transport medium composition may affect the absorption of compounds during in vitro drug transport testing. To preserve the predictive values of screening tests, the possible influence of transport media on the solubility of model drugs and on the activities of tight junctions and efflux transporter proteins (e.g., Pglycoprotein) must be known. Objective: The aim of this study was to compare the impact of different transport media on the bidirectional transport of standard compounds, selected from the four classes of the Biopharmaceutical Classification System (BCS), across excised pig intestinal tissue. Methods: The Sweetana-Grass diffusion apparatus was used for transport studies. Krebs-Ringer bicarbonate (KRB) buffer and simulated intestinal fluids in the fed (FeSSIF) and fasted (FaSSIF) states were used as the three transport media, while the chosen compounds were abacavir (BCS class 1), dapsone (BCS class 2), lamivudine (BCS class 3) and furosemide (BCS class 4). Results: Abacavir exhibited lower permeability in both the simulated intestinal fluids than in the KRB buffer. Dapsone showed similar permeability in all media. Lamivudine exhibited lower permeability in FaSSIF than in the other two media. Furosemide exhibited improved transport with pronounced efflux in FaSSIF. Conclusion: Different permeation behaviors were observed for the selected drugs in the respective media, which may have resulted from their different physico-chemical properties, as well as from the effects that dissimilar transport media components had on excised pig intestinal tissue.

Background: Eplerenone (EPL) is a BCS class II drug, thus, having poor water solubility. The poor water solubility of this drug leads to poor dissolution and ultimately shows poor bioavailability. To overcome this problem, the solid dispersion of EPL was prepared in this study. Methods: This was accomplished by using the solvent melt method as the solid dispersion technique. In this method, Pluronic F-68 and F-127 were used as the carrier and different formulations were prepared using varying ratios of a drug and carrier (1:1, 1:2, 1:3, 1:4, 1:5). The mixture of drug solution and carrier was prepared at 70°C, using the digital magnetic stirrer. The resultant mixture was dried at 40°C in a hot air oven and optimized EPL-solid dispersion was undergone for their characterization using drug content, drug entrapment efficiency (%) and drug loading content (%), Scanning Electron Microscopy (SEM), Infra-Red spectroscopy, Differential Scanning Calorimetry (DSC), stability study and in-vitro dissolution studies. Results: The result indicated that there was no interaction between EPL and Pluronics (Pluronic F-68 & F-127), and optimized formulation (P127-2) of EPL-solid dispersion had encapsulation efficiency > 95%. Experimental work also showed that optimized formulation has 31.7% of drug loading content which was greater than other existing solid dispersion having less than 30% of drug loading content. Out of different batches, the optimized batch exhibits the faster dissolution rate in comparison to other batches. It released the almost total amount of drug (98.96%) in 30 minutes. The stored ESM-solid dispersion also exhibited remarkable stability and remains in a solid state, when it was exposed to 25°C/60% relative humidity and room temperature (38ºC) for two months. Such stability was confirmed by DSC method. The DSC thermogram of optimized formulation exhibited a melting endotherm at an onset temperature of 160°C, a peak temperature of 165°C and a heat of fusion of 25.68 J/gm. Similarly, the DSC thermogram of the physical mixture of bulk EPL/- pluronic F-127 also exhibited the onset of temperature at 165°C, and a peak temperature at 171°C. Thus, the result indicated that both samples showed almost similar DSC pattern and no sample altered its state after the treatment of temperature and humidity used in stability testing. SEM study was also performed in this research and the result indicated that the particle size of optimized formulation was varied, having irregular matrices due to the porous nature of the carrier. Conclusion: Based on different findings, it can be concluded that the solvent melt method could be a potential method for preparing the solid dispersion of EPL like BCS class-II Drugs and will be able to solve the dissolution and solubilization related problem of poorly soluble drugs.

Background: Periodontitis is one of the most widespread oral diseases. Curcumin, a hydrophobic polyphenolic compound derived from the rhizomes of Curcuma longa has a great potential for biological and pharmacological activities. The introduction of local controlled delivery of curcumin directly into the periodontal pocket is a promising approach for the treatment of periodontitis. Objective: The study has been designed to formulate intrapocket dental film loaded with curcumin to be used for insertion into the periodontal pockets and evaluate its clinical efficacy. Methods: Curcumin dental films were prepared by the solvent casting technique using polymers such as Ethylcellulose, HPMC K4M, Eudragit RL 100, Chitosan with Dibutyl Phthalate and Poly Ethylene Glycol 400 as the plasticizer. The prepared films (CDF1-CDF16) were evaluated for various physicochemical parameters employing established pharmaceutical procedures such as surface pH, folding endurance, tensile strength, swelling index, drug content, in-vitro drug release, antibacterial efficacy, stability studies, and clinical efficacy. Results: Experimental parameters of the obtained film exhibited results within the desired limit. Fourier Transform Infrared Spectroscopy and Differential Scanning Calorimetry studies revealed the formulated film to be stable during drug stability and compatible between drugs and excipients. The surface morphology of the formulation using Scanning Electron Microscope images showed the presence of free drug particles on the surface, causing a burst effect at the desired site. In-vitro dissolution studies showed an initial burst release to achieve an immediate therapeutic level of drug in the periodontal pocket followed by a progressive fall and extended-release of the drug for 10 days. The therapeutics effects, such as antibacterial activity of films on P. gingivalis, were also observed. Furthermore, the clinical trials of formulation CDF16 on affected patients proved the therapeutic efficacy of the dental films showing a statistically significant (p < 0.05) decrease in the clinical markers of periodontitis, i.e. periodontal probing depth, plaque index, and sulcular bleeding index. Conclusion: The experimental results suggest that Curcumin dental film can be experimentally identified as a potential drug delivery device. Hence, curcumin dental film can be used for topical treatment of periodontal diseases and to achieve optimum therapeutic efficacy.