Drug Delivery Letters - Volume 11, Issue 2, 2021

The delivery of therapeutic agents through the oral route remains the most favorable one as compared to other routes of drug administration. However, numerous disadvantages are encountered in conventional formulations such as low bioavailability, first-pass metabolism, gastric irritation, delayed onset of action, bitter taste, low retention time, frequent dosing, and non-localized drug targeting. All these problems encountered guide the various pharmaceutical industries to manufacture and develop a novel solid oral dosage form called lozenges. Lozenges are solid oral dosage forms of medicament, meant to be dissolved within the mouth or pharynx. They may consist of one or more than one medicinal agent in a sweetened and flavored base material. The present review is focused on various types, compositions, and methodologies used to prepare the medicated lozenges and on different evaluation parameters that establish their safety and efficacy. It also put a light on different commercially available and reported medicated lozenges formulation. The various review and research articles reported by different researchers were studied extensively by using the databases of Google Scholar, Pubmed, Scopus, Web of Science and various commercial websites that were also investigated for information regarding new products. Lozenges provide various advantages in terms of patient compliance, rapid onset of action, prolonged retention time, enhancement of bioavailability, ease of manufacturing, localized drug targeting, sustained or controlled effect, and reduced dosing frequency. They also have the ability to incorporate the drugs belonging to different therapeutic classes for treating various disorders related to oral cavities like gingivitis, dental plaque, mouth ulcers, throat pain, oral thrush, throat infection, periodontitis, and pharyngitis. However, its applicability is not only limited to localized action, but it has also been employed to deliver the drug systemically for the conditions such as cough, decongestion, runny nose, nausea, vomiting, allergy, low immunity, fever, body ache, the killing of worms and smoking cessation. It was concluded that they have played an important role in the field of drug delivery and will continue to perform in the same way in the future as well.

Colon-targeted drug delivery technology; an approach of immense potential, has acquired tremendous significance for managing a number of ailments, particularly of the colon and for delivering therapeutic proteins and peptides systemically. The major hurdles for delivering drugs in the colonic region include absorption and degradation pathways in the upper gastrointestinal tract (GIT). To achieve a triumphant colonic delivery, the therapeutic agent must be protected from getting absorbed in the preliminary region of GIT to ensure its release in the proximal colon in a controlled way. The principle approaches, for instance, prodrug approach, pH sensitivity, timedependency (lag time), degradation by microbes, etc. have been effectively applied for obtaining colon targeted drug delivery. These approaches have accomplished immense relevance. Therefore, incessant attempts have been mainly focused on the design of colon targeted drug delivery systems having enhanced site-specificity along with the study of its versatile drug release kinetics to achieve diverse therapeutic requirements. The current manuscript illustrates the significance of different colon drug delivery systems and general considerations for designing colon targeting systems, including primary as well as novel approaches. Recent investigational studies carried out by scientific communities worldwide for the designing and preparation of various colon-targeted formulations along with their significant insights have been described. Recent patents, structure-property relationship and dissolution aspects pertaining to the colon-specific drug delivery have also been depicted.

The low solubility of an active pharmaceutical ingredient particularly biopharmaceutics classification system (BCS) Class II drugs leads to a lower dissolution profile, which in result causes a reduction in the overall bioavailability of drugs. Numerous approaches like nanotechnology, solid dispersion technique, micronization techniques, etc were aimed by scientists in the past to resolve this issue, but still not enough to get the desired outcomes. Key focus of this review is the study of the advantages and disadvantages of cocrystallization, nanotechnology and solid dispersions drug delivery techniques and the benefits of using cocrystallization techniques over the above-mentioned techniques. Various parameters including pharmaceutical, pharmacological and toxicological effects related to these mentioned drug delivery systems have been compared. Their advantages and disadvantages have been elaborated. For drug delivery purpose, the cocrystallization process has numerous advantages over nanotechnology and solid dispersions drug delivery techniques discussed in the text. Cocrystallization is a newer technique that can modify the physicochemical and pharmaceutical properties of active pharmaceutical ingredients (API) with low solubility, low stability or sensitivity toward environmental hazards like temperature, moisture or photostability issues. During cocrystallization, the drug and the coformer interact with each other non-covalently in a fixed stoichiometric ratio. The availability of a large number of coformers makes this technique to be favorable for the researchers in designing cocrystals of newer and older API’s. Although solid dispersions and nanotechnology techniques are being utilized to a larger extent, still there are some drawbacks of these techniques like stability, toxicological factors and protection from environmental factors that need to be considered, while the cocrystallization process drastically modifies the various pharmaceutical parameters without altering the pharmacological properties of API’s. Here in this review, we performed a comparative analysis between nanotechnology, solid dispersion and cocrystallization techniques along with the importance of cocrystallization in the modification of drug profile and various applications in the pharmaceutical and allied industry.

Targeting drugs with controlled release characteristics to the colon is gaining importance for localized action as well as to improve the systemic availability of peptides and proteins. The present manuscript aims to describe the various approaches and model studies for colon targeted drug delivery. Drugs that have low absorption windows are targeted to the colonic regions using different novel technologies such as microparticulate systems, prodrugs, pH and time-dependent polymeric, effervescent and non-effervescent systems, etc. Along with this, this manuscript also describes the model study for colon targeting. Colon targeted drug delivery system offers the potential therapeutic benefits to patients in terms of both local and systemic treatment. These drugs can be directly targeted to the colon, which helps in reducing the systemic side effects.

Background: In 1988, the US Food and Drug Administration permitted low dose methotrexate for the treatment of rheumatoid arthritis that would change the progression of the disease. Methotrexate is a folic acid antagonist and its systemic use causes numerous side effects; including hepatic toxicity. It would be preferable to deliver methotrexate by the topical route to reduce side-effects along with ease of administration and reduced dosing frequency. So, nanoparticle gel is a hopeful approach to treat rheumatoid arthritis. Objective: The study aims to develop a nanoparticles gel containing novel natural polymer-based methotrexate nanoparticles and evaluate its therapeutic potential on Complete Freund’s Adjuvant– Induced Arthritis rat model and compare it to methotrexate and dexamethasone gel. Materials and Methods: The five batches of methotrexate nanoparticles gel were prepared viz. F1W2, F2W2, F3W2, F4W2 and methotrexate gel for the topical application by using different concentrations of Carbopol 934 base and characterized for their evaluation parameters: homogeneity, grittiness, pH, spread-ability, viscosity determination, and drug content studies. The arthritic potential of methotrexate-nanoparticles gel was evaluated by Complete Freund’s Adjuvant–Induced Arthritis rats model based on percent inhibition oedema and arthritic score. Result and Discussion: Methotrexate nanoparticles gel significantly reduced the percentage inhibition of oedema compared to methotrexate and dexamethasone gel. The therapeutic activity of nanoparticles gel was found to be F3W2 ≥ F2W2 ≥ F1W2 ≥ F4W2 ≥ MTX gel. So, the optimized nanoparticle gel formulation F3W2 can be effective in the treatment of rheumatoid arthritis. Conclusion: The developed novel nanoparticles gel formulation can be a promising alternative to existing methotrexate and dexamethasone gel.

Background: Multiple dosing is required for bosentan in order to achieve steady-state concentration. Hence formulating bosentan controlled release formulation could be an approach to solve this issue. Objective: The objective is to develop floating multiple unit minitablets of bosentan using the Quality by design approach. Methods: Failure mode effect analysis (FMEA) and Taguchi design are employed in order to screen highly critical factors. Box-Behnken design (BBD) was adopted for the process of optimization. Results: The quantity of gelucire 39/01, HPMC K15 M, and sodium bicarbonate was found to be one of the significant factors using Taguchi design. The Box-Behnken design results in the optimised formulation showing floating lag time within 3 min, floating time of nearly 15 h, time to release 50% of drug of 3.6 h, time to release 90% of drug of 11h and better bioavailability compared to pure drug. Conclusion: It can be concluded that floating multiple unit minitablet can be used as an encouraging approach for sustaining the drug release of bosentan.