Drug Delivery Letters - Volume 11, Issue 3, 2021

The objective of the present article is to review various aspects of dissolution studies of dosage forms performed with the flow-through apparatus (USP type-IV apparatus). USP type-IV apparatus is comprised of a pump that compels the dissolution media upwards via the flow-through cell. A reservoir of dissolution medium is attached to the cell that is mounted vertically with a filter system to restrain the escape of un-dissolved particles. The apparatus is specially designed for powders, microparticles, pellets and tablets. In this type of in vitro dissolution method, the test sample is placed in the bottom of the small-volume flow-through cell; the solvent passes through it at a temperature of 37°C. This study is very important to build up the in-vivo and in-vitro relationship. Likewise, this study is used to distinguish the extent of medication released from the tested sample so as to foresee its in vivo viability in actual patient population. The flow-through cell is used to determine the dissolution of micro-particulate, suppositories, implants, controlled-release formulations with drugs that have very low aqueous solubility. The drugs with small particle size and large surface area are dissolved at a faster rate as compared to other existing and compendial dissolution apparatuses. The article also highlights some of the in vitro dissolution studies carried out with the USP type-IV apparatus.

The eye is the most important sensory organ, which restricts most of the active substances due to its static and dynamic barriers. The application of conventional eye drop is still popular, but it was found to be less permeable to both anterior and posterior eye portions, requiring more frequent administration. It seems to be a great challenge for the researcher to fabricate an ocular formulation that crosses the barriers and achieves an optimal therapeutic concentration at the ocular globe. Recent studies revealed that a nanostructured lipid carrier has great potential in ophthalmic use and has become more popular due to its permeability in the eye cavity. This review describes the nanostructured lipid carriers with respect to the mechanism of ocular permeation, structural feature, manufacturing process, characterization, and its merits over other nanocarriers. In recent years, newly nanostructured-based ocular formulations have been developed, like surface-modified with various cationic compounds and their integration with different polymeric systems, to enhance ocular bioavailability in both regions of the eye. Newly developed nanostructured lipid carriers include surface modified cationic lipid, polymers, and thiolated compounds, etc., that increases mucoadhesive property. Finally, nanostructured incorporated forms, in situ gel, and hydrogel increase permeation in the posterior region of the eye.

Critically challenging tasks for the researchers are isolating and extracting chief active medicinal phytoconstituents from existing herbal plants. The intricate extraction process usually involves active plant and animal portions separated by selective solvents through various standard procedures. Therefore, most of the products contained the complex metabolites mixtures, making the extraction process involved in separating these products increasingly tricky, thus resulting in lesser yield. Therefore, an alternative strategy suitable for green extraction routes has recently succeeded as a sustainable resource with many advantages like high solvency, low toxicity, and low impact in the environment, biodegradable, and helps recycle consumed solvents without showing any detrimental effects on the environment. The process of green hydrotrope-assisted extraction process persists a novel and promising methodology that maximizes the yield of phytoconstituents in comparison to the conventional extraction process by the commissioning of a variety of hydrotropes like sodium cumene sulfonate, sodium alkyl-benzene sulfonates, and sodium butyl mono-glycol sulfate, involved in selective extraction of water-insoluble phytoconstituents by the disorganization of the phospholipid bilayers by the hydrotrope, through cell permeabilization, disruption of the cellulosic cell wall and, then possibly the dissolution of the cellular contents. The central point of this audit is the increase of the surrender of phytoconstituents from herbal plants accomplished by considering green hydrotropic-assisted extraction process, an assignment of carrying out the extraction of herbal plants sanctioning hydrotropes and its component. Using hydrotropes for extracting the phytoconstituents has imperatively highlighted the conveyance frameworks of separated extricated phytoconstituents from herbal plants and encourages the forwarding of their bioavailability at distinctive target destinations.

Aim: The aim of the present work is the implementation of Quality by Design principles for the evolution of optimized sustained release drug delivery system. Background: Quality by Design (QbD) approach refers to an advance approach to develop an optimized dosage form. QbD has become a vital modern scientific approach to develop a quality dosage form. In the modern era of science, researchers can develop an optimized dosage form with least effort, money and manpower. Objectives: Objective of the research work was the successful development of optimized floating bioadhesive tablets of glipizide using floating-bioadhesive potential of cellulosic polymer and carbomersusing quality by design (QbD) approach. Methods: Quality Target Product Profile (QTPP) of drug delivery system was defined as well as critical quality attributes (CQAs) were identified. A face centered central composite design (CCD) was utilized in assessing the impact of the individual critical material attribute (CMA) like Hydro Propyl Methyl Cellulose K4M(HPMC K4M)and Carbopol 934P (CP 934P) and their interactions, using least experimentation. Formulations were developed and quantitative impact on CQAs was determined using mathematical model. The optimized formulation was obtained and characterized for in-vitro as well as in-vivo parameters. Results: A Fishikawa diagram and Failure Mode and Effect Analysis (FMEA) was performed to identify potential failure modes associated with the dosage form. The optimum formulation was embarked upon using mathematical model developed yielding desired CQAs followed for confirmation of data. Sustained release drug delivery system was successfully developed by using QbD approach. In-vivo X-ray imaging in rabbit and γ-scintigraphic study in manconfirmed the buoyant nature of the mucoadhesive floating tablet for 8 h in the upper gastrointestinal tract. Conclusion: Optimized formulation shows phenomenal floating, bioadhesive properties and drug release retardation characteristics, utilizing a mixture of cost-effective polymers Hence, QbD approach may be regarded as an important tool in development of floating bioadhesive CR dosage forms.

Background: The better control of the drug release with immediate effect is the major concern to achieve better therapeutic action and patient compliance. The failure of the solid dispersion complex during storage as well as in-vivo is another concern for the oral solid dosage form. Objective: The prime objective of the present study was to optimize the biphasic minitablet incorporating quality by design approach using the combination of waxy erodible and water-impermeable excipients. Exploration of Soluplus as a precipitation inhibitor and Dexolve as a solubility enhancer in oral solid dosage form was the secondary objective. Methods: The drug-Excipient compatibility study was assessed by FTIR. Clozapine was chosen as a model drug that has poor aqueous solubility. The complex was formulated using B-cyclodextrin or HP B-CD or Dexolve by kneading method. The screening of solubility enhancers and their amount were performed based on phase solubility study. The precipitation inhibitor was screened as per the parachute effect study. Immediate release minitablets were formulated using a direct compression method using different disintegrating agents. The IR minitablets were evaluated for different evaluation parameters. The sustained release minitablets were formulated by hot-melt granulation technique incorporating the Precirol ATO 5 as a waxy excipient and ethyl cellulose as water impermeable excipient. The SR minitablet was optimized using a central composite design. The amount of Precirol ATO 5 and ethyl cellulose were chosen as independent variables and % drug release at 1, 6, and 10 h was selected as responses. The designed batches were evaluated for different pre and post-compressional parameters. The IR and SR minitablets were filled in a capsule as per dose requirement and evaluated for in-vitro drug release. The in-vivo plasma concentration was predicted using the Back calculation of the Wagner - Nelson approach. Results: Drug - Excipient study revealed that no significant interaction was observed. Dexolve was screened as a solubility enhancer for the improvement of the solubility of clozapine. The Soluplus was chosen as a precipitation inhibitor from the parachute effect study. The immediate-release tablet was formulated using Prosolv EASYtab SP which yielded less disintegration time with better flowability. The sustained release mini-tablet was formulated using Precirol ATO 5 and ethyl cellulose. Two-dimensional and three-dimensional plots revealed significant effect of the amount of Precirol ATO 5 and ethyl cellulose. The overlay plot locates the optimized region. The in-vitro drug release study revealed the desired drug release of the final combined formulation. The in-vivo plasma concentration-time confirms the drug release up to 12h. Conclusion: The biphasic mini-tablets were formulated successfully for better control of drug release leads to high patient compliance. The use of soluplus as a precipitation inhibitor is explored in the oral solid dosage form for a poorly aqueous drug. Prosolv EASYtab SP was incorporated in the formulation as super disintegrant. The amount of Precirol ATO 5 and ethyl cellulose significantly affected drug release in sustained-release minitablet. The approach can be useful in the industry.

Background: Acyclovir, BCS Class III drug is commercially available as 3% w/w eye ointment for multiple applications. Acyclovir nanoemulsions can be proposed to reduce dose because of improved permeation characteristics. Further, the development of in situ ophthalmic gels can be advantageous to reduce the number of applications due to increased mucoadhesion and sustaining effect. Objective: The purpose of this study was the development and evaluation of nanoemulsions based in situ gels of Acyclovir (1% w/w) as potential ophthalmic delivery systems. Methods: Nanoemulsions of Acyclovir were developed by Phase Inversion Temperature method using Capmul MCM, stearyl amine and Kolliphor RH 40 as liquid lipid, charge inducer and surfactant, respectively selected on the basis of Acyclovir solubility in the oil phase and emulsification ability of surfactants. These nanoemulsions were further developed into in situ ophthalmic gels using gellan gum and Methocel K4M. Results: The developed gels showed a sustained effect in vitro release studies and improved goat corneal permeation in ex vivo studies when compared to marketed ointment. HET-CAM studies concluded the absence of irritation potential, while in vivo irritation study in Wistar rats showed the absence of erythema and swelling of eyes after visual inspection for 72 hours. Histopathological studies on isolated rat corneas showed no abnormalities in anterior corneal epithelium and corneal stroma without any epithelial hyperplasia. Acyclovir nanoemulsions based in situ ophthalmic gel showed increased corneal deposition and permeation in isolated rat eyes. Conclusion: The improved potential of developed ophthalmic gels was proven due to the reduced frequency of application compared to the marketed ointment in animal studies.