Recent Advances in Drug Delivery and Formulation - Volume 18, Issue 2, 2024

Amorphous Solid Dispersions (ASDs) have indeed revolutionized the pharmaceutical industry, particularly in drug solubility enhancement. The amorphous state of a drug, which is a highenergy metastable state, can lead to an increase in the apparent solubility of the drug. This is due to the absence of a long-range molecular order, which results in higher molecular mobility and free volume, and consequently, higher solubility. The success of ASD preparation depends on the selection of appropriate excipients, particularly polymers that play a crucial role in drug solubility and physical stability. However, ASDs face challenges due to their thermodynamic instability or tendency to recrystallize. Measuring the crystallinity of the active pharmaceutical ingredient (API) and drug solubility is a complex process that requires a thorough understanding of drug-polymer miscibility and molecular interactions. Therefore, it is important to monitor drug solids closely during preparation, storage, and application. Techniques such as solid-state nuclear magnetic resonance (ssNMR), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), Raman spectroscopy, and dielectric spectroscopy have been successful in understanding the mechanism of drug crystallization. In addition, the continuous downstream processing of drug-loaded ASDs has introduced new automated methods for consistent ASD production. Advanced techniques such as hot melt extrusion, KinetiSol, electro spraying, and electrospinning have gained popularity. This review provides a comprehensive overview of Amorphous Solid Dispersions (ASDs) for oral drug delivery. It highlights the critical challenges faced during formulation, the impact of manufacturing variables, theoretical aspects of drug-polymer interaction, and factors related to drug-polymer miscibility. ASDs have been recognized as a promising strategy to improve the oral bioavailability of poorly water-soluble drugs. However, the successful development of an ASD-based drug product is not straightforward due to the complexity of the ASD systems. The formulation and process parameters can significantly influence the performance of the final product. Understanding the interactions between the drug and polymer in ASDs is crucial for predicting their stability and performance.

In recent times, technological and scientific advances have been made in studying and developing orally delivered medication. Such studies demonstrate the importance of the oral route among patients. The accuracy of drug delivery is very important to achieve a successful therapeutic effect in the case of various pharmaceutical products. A novel drug delivery system adds new benefits or advantages to a drug. This review covers all the aspects of medicated chewing gum (MCG) as a new drug delivery method, including the benefits and drawbacks, manufacturing methods, type of MCG, composition of chewing gum, evaluation parameters, factors that affected the release of API, its pharmaceutical significance, various marketed chewing gum and chewing gum packaging. Chewing gum as a drug delivery system has the potential to cure or prevent various indications, such as analgesic, CNS stimulation, smoking cessation, motion sickness, and treatment and prevention of dental caries or gingivitis. Pharmaceutical distribution to the oral mucosa can be made more convenient and enticing with the help of MCG. Compared to conventional techniques, this delivery system has a longer-lasting effect, which makes it a viable option for treating digestive problems, headaches, migraines, coughing, anxiety, and allergies.

Objective: The primary limitations of tadalafil in treating erectile dysfunction are its low solubility and unpleasant bitter taste, which ultimately result in inadequate patient adherence. The present study aimed to develop and characterize a medicated chocolate formulation containing Tadalafil and β-CD (solubility enhancer) employing the concept of Design of Experiment (DoE) using chocolate as a user-friendly excipient. Methods: An inclusion complex was formulated by incorporating the drug into β-CD using the kneading method for solubility improvement and also as a taste masker for Tadalafil. The ratio of drug: β-CD inclusion complex was selected based on a phase solubility study. The inclusion complex was molded into a chocolate base and optimized using the DoE approach. Further, drug excipient interaction was evaluated by DSC and FTIR study. Results: Phase solubility study suggested a 1:1 ratio of Tadalafil: β-CD for better solubility. DSC spectra suggested the conversion of crystalline structure into an amorphous state which indicates improvement of the drug solubility. DSC and FTIR studies revealed that there was no significant interaction between drug and excipients. Next, %CDR (cumulative drug release) at 30 min revealed the immediate effect of Tadalafil from chocolate formulation and free drug analysis (an unbound drug with β-CD) proved reduced bitterness of the drug in the complex. Additionally, the medicated chocolate was found to be stable at room temperature as per stability study. Conclusion: β-CD was found to be a promising multifunctional excipient as a solubility enhancement carrier and taste masker for bitter-tasting drugs.

Background: Crisaborole (CB), a boron-based compound, is the first topical PDE4 inhibitor to be approved by the US Food and Drug Administration (2016) for the treatment of Atopic Dermatitis. It is marketed as a 2% ointment (Eucrisa, Pfizer). However, CB is insoluble in water; therfore, CB glycersomes were formulated to enhance its permeation flux across the skin. Objective: We developed a glycerosomal gel of CB and compared its in vitro release and permeation flux with the 2% conventional ointment. Methods: Glycerosomes were prepared using thin film hydration method employing CB, soya phosphatidylcholine, and cholesterol. The formed film was further hydrated employing a mixture of phosphate buffer pH 7.4 /glycerin solution containing varying percentages (20,30, 40, and 50 %) of glycerol. The glycerosomes obtained were characterized by their size, polydispersity index (PDI), and Zeta potential. The entrapment efficiency of the optimized formulation (F1) was determined. The in vitro release of F1 was compared with its 2% conventional ointment. F1 was further incorporated into carbopol 934 P gel. The gel was characterized by pH, viscosity, spreadability, and drug content. The permeability flux of the glycerosomal gel was compared with its 2% conventional ointment. Results: The optimized CB glycerosomes had a vesicle size of 137.5 ± 50.58 nm, PDI 0.342, and zeta potential -65.4 ± 6.75 mV. CB glycerosomal gel demonstrated a 2.13-fold enhancement in the permeation flux. Conclusion: It can thereby be concluded that glycerosomes can be an effective delivery system to enhance the penetration of CB across the skin.

Background: Probiotics must be able to withstand the demanding environment of the gastrointestinal system to adhere to the intestinal epithelium, promoting health benefits. The use of probiotics can prevent or attenuate the effects of dysbiosis that have a deleterious effect on health, promoting anti-inflammatory, immunomodulatory, and antioxidant effects. Objective: The aim of the study was to prepare tablets containing Lactobacillus fermentum LF-G89 coated with 20% Acryl-Eze II^® or Opadry^® enteric polymers. Methods: Tablet dissolution was evaluated under acidic and basic pH conditions, and aliquots of the dissolution medium were plated to count the Colony-forming Units (CFU). The free probiotic's tolerance to pH levels of 1.0, 2.0, 3.0, and 4.0, as well as to pepsin, pancreatin, and bile salts, was assessed. Results: The probiotic was released from tablets coated after they withstood the pH 1.2 acid stage for 45 minutes. The release was higher with the Acry-Eze II^® polymer in the basic stage. The amount of CFU of free probiotics at pH 1.0 to 4.0 as well as pepsin reduced over time, indicating cell death. Conversely, the CFU over time with pancreatin and bile salts increased, demonstrating the resistance of L. fermentum to these conditions due to hydrolases. Conclusion: Both coating polymers were able to withstand the acid step, likely ensuring the release of the probiotic in the small intestine, promoting colonization. Coating with enteric material is a simple and effective process to increase the survival of probiotics, offering a promising alternative to mitigate the negative effects of the dysbiosis process.

Background: Nanophytosomes represent an effective choice for topical drug delivery systems thanks to their small size, general non-toxicity, ease of functionalization and high surface to volume ratio. The goal of the current study was to investigate the potential benefits of using Hypericum perforatum extract nanogel as a means of improving skin penetration and prolonging skin deposition in dermatitis similar to psoriasis. Methods: Nanophytosomes (NPs) were developed, optimised and thoroughly characterised. The optimised NPs were then placed in a Carbopol gel base matrix and tested ex-vivo (skin penetration and dermatokinetic) and in-vivo (antipsoriatic activity in an Imiquimod-induced psoriatic rat model). Results: The optimised NPs had a spherical form and entrapment efficiency of 69.68% with a nanosized and zeta potential of 168 nm and -10.37mV, respectively. XRD spectra and transmission electron microscopy tests confirmed the plant botanical encapsulation in the NPs. Following 60 days of storage at 40 ± 2°C/75 ± 5% RH, the optimised formula remained relatively stable. As compared to extract gel, nano-gel showed a much-improved ex vivo permeability profile and considerable drug deposition in the viable epidermal-dermal layers. When developed nano-gel was applied topically to a rat model of psoriasis, it demonstrated distinct in vivo anti-psoriatic efficacy in terms of drug activity and reduction of epidermal thickness in comparison to other formulations and the control. ELISA and histopathologic studies also demonstrated that nano-organogel had improved skin integrity and downregulated inflammatory markers (IL-17, IL-6, IFN-γ and MCP-1). Conclusion: Findings suggest that a developed plant botanicals-based nanogel has a potential for the treatment of psoriasis-like dermatitis with better skin retention and effectiveness.