The advanced in silico simulation tools, such as physiologically based biopharmaceutics models (PBBM) or physiologically based pharmacokinetic models (PBPK), play critical role in model informed formulation development. This approach has been successfully implemented in the present case for development of novel omeprazole delayed-release orally disintegrating tablets (ODT) formulation, aimed to enhance patient compliance.PBBM was developed using physicochemical, biopharmaceutical, and dissolution data. The dissolution studies for pilot formulations were conducted in bio predictive media in fasting (0.1N HCl followed by pH 6.8) and fed (pH 5 followed by pH 6.8) conditions. The model was extensively validated in three stages: pilot fasted, pilot fed virtual bioequivalence and food effect assessments. Impressively, the model was able to predict both passed and failed batches appropriately.Based on insights from the pilot study, a higher scale pivotal formulation was optimized. Prospective predictions were made for pivotal formulations using validated model and bio results were found to be in line with model predictions in fasting condition.Overall, a rationale and patient compliant formulation was developed using innovative modeling approach and filed to regulatory agency. The novel omeprazole formulation enhanced patient compliance through ease of administration thereby circumventing challenges of conventional formulation.

This study explores the realm of personalized medicine by investigating the utilization of 3D-printed dosage forms, specifically focusing on patient-specific enteric capsules designed for the modified release of ketoprofen, serving as a model drug. The research investigates two distinct scenarios: the modification of drug release from 3D-printed capsules crafted from hydroxypropyl methylcellulose phthalate:polyethylene glycol (HPMCP:PEG) and poly(vinyl alcohol) (PVA), tailored for pH sensitivity and delayed release modes, respectively. Additionally, a novel ketoprofen-loaded self-nanoemulsifying drug delivery system (SNEDDS) based on pomegranate seed oil (PSO) was developed, characterized, and employed as a fill material for the capsules. Through the preparation and characterization of the HPMCP:PEG based filament via the hot-melt extrusion method, the study thoroughly investigated its thermal and mechanical properties. Notably, the in vitro drug release analysis unveiled the intricate interplay between ketoprofen release, polymer type, and capsule thickness. Furthermore, the incorporation of ketoprofen into the SNEDDS exhibited an enhancement in its in vitro cylooxygenase-2 (COX-2) inhibitory activity. These findings collectively underscore the potential of 3D printing in shaping tailored drug delivery systems, thereby contributing significantly to the advancement of personalized medicine.

Gallic acid-Antarctic krill peptides (GA-AKP) nanocapsules (GA-AKP-Ns) were prepared using a dual delivery system with complex emulsion as the technical method, a high-pressure microjet as the technical means, polylactic acid-hydroxyacetic acid (PLGA) as the drug delivery vehicle, and GA-AKP as the raw material for delivery. This study aimed to investigate the effects of microjet treatment and the concentration of PLGA on the physicochemical properties and stability of the emulsion. Under optimal conditions, the physicochemical properties and hypoglycemic function of nano-microcapsules prepared after lyophilization by the solvent evaporation method were analyzed. Through the microjet treatment, the particle size of the emulsion was reduced, the stability of the emulsion was improved, and the encapsulation rate of GA-AKP was increased. The PLGA at low concentrations decreased the particle size of the emulsion, while PLGA at high concentrations enhanced the encapsulation efficiency of the emulsion. Additionally, favorable results were obtained for emulsion preparation through high-pressure microjet treatment. After three treatment cycles with a PLGA concentration of 20 mg/mL and a microjet pressure of 150 MPa (manometric pressure), the emulsion displayed the smallest particle size (285.1 ± 3.0 nm), the highest encapsulation rates of GA (71.5%) and AKP (85.2%), and optimal physical stability. GA-AKP was uniformly embedded in capsules, which can be slowly released in in vitro environments, and effectively inhibited α-amylase, α-glucosidase, and DPP-IV at different storage temperatures. This study demonstrated that PLGA as a carrier combined with microjet technology can produce excellent microcapsules, especially nano-microcapsules, and these microcapsules effectively improve the bioavailability and effectiveness of bioactive ingredients.

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.
CONCLUSIONS: 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.

Solid dispersion (SD) technology is one of the most widely preferred solubility enhancement methods, especially for Biopharmaceutics classification system class II and IV drugs. Since the last decade, its application for the dual purpose of solubility hike and modified release using novel carriers has been in demand for its added advantages. Spray drying is a commercially accepted technique with high aspects of scalability and product characteristics. The current study used spray-dried dispersion to design delayed release capsule for the proton pump inhibitor esomeprazole. The SD carrier hydroxypropyl methylcellulose acetate succinate-medium grade (HPMCAS-MF) enhanced solubility, inhibited precipitation of saturated drug solutions, and allowed enteric release owing to its solubility above pH 6. The proposed approach avoided compression, coating with enteric polymers, and the development of multi-particulate pellet-based formulations, improving manufacturing feasibility. The formulation was optimized using Box-Behnken design, considering significant formulation variables like HPMCAS-MF proportion and critical process parameters like feed flow rate and inlet temperature. The optimized spray-dried dispersion were characterized based on Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM) and also evaluated for solubility, in vitro drug release, residual solvent content, and stability testing. Response surface methodology optimization anticipated that formulation variables affected solubility and release profile, whereas CPPs affected yield. The design space was developed via overlay plot based on constraints specified to attain the desired response and validated using three checkpoint batches with desirability 1. FTIR showed active pharmaceutical ingredient-polymer compatibility. Particle size and SEM studies showed spherical particles with an average Z-value of 1.8 µ. DSC and PXRD confirmed SD\'s amorphous nature. The drug release investigation and release kinetics prediction utilizing DD-solver software showed a 2-h lag time with > 90% cumulative drug release up to 4 h for the DR formulation. ESM SDD were prepared by spray drying technique using the novel solid dispersion carrier HPMCAS-MF to serve the dual purpose of solubility enhancement and delayed release. The ratio of API:carrier and process variables like feed flow rate and inlet temperature were varied using the Box-Behnken Design to determine the design space of optimized product to procure the desired characteristics of solubility improvement compared to crystalline API and delayed release of PPI to avoid the degradation in the gastric environment. The developed formulation represents several benefits over the already existing marketed products.

A satisfactory drug release profile for gonadotropin-releasing hormone (GnRH) agonist drugs is high initial release followed by small amount of drug release per day. In the present study, three water-soluble additives (NaCl, CaCl2 and glucose) were selected to improve the drug release profile of a model GnRH agonist drug-triptorelin from PLGA microspheres. The pore manufacturing efficiency of the three additives was similar. The effects of three additives on drug release were evaluated. Under the optimal initial porosity, the initial release amount of microspheres containing different additives was comparable, this ensured a good inhibitory effect on testosterone secretion in the early stage. For NaCl or CaCl2 containing microspheres, the drug remaining in the microsphere depleted rapidly after the initial release. The testosterone concentration gradually returned to an uncontrolled level. However, for glucose containing microspheres, it was found that the addition of glucose could not only increase the initial release of the drug but also assist in the subsequent controlled drug release. A good and long-time inhibitory effect on testosterone secretion was observed in this formulation. The underlying cause why the incorporation of glucose delayed the subsequent drug release was investigated. SEM results showed that considerable pores in glucose containing microspheres were healed during the microspheres incubation. After thermal analysis, an obvious glass transition temperature (Tg) depression was observed in this formulation. As Tg decreased, polymer chains are able to rearrange at lower temperatures. This, morphologic change was reflected in the gradual closure of the pores, and is the likely reason that drug release slowed down after the initial release.HIGHLIGHTSThe addition of glucose could not only increase the burst release of the drug but also delay the subsequent drug release.High initial burst and a sustained drug release helped obtain a good inhibitory effect on testosterone secretion.As Tg decreased, polymer chain was prone to rearrange. Morphologic change was reflected in the gradual closure of the pores. This was the reason that drug release slowed down after the initial burst.

The objective of this study was to propose a new coating film for biodegradable polymers and environmentally friendly processing. Here, a novel implementation of solid lipid nanoparticles (SLN) into a biodegradable alginate (ALG) film composition created a new gastric-resistant film for an enteric-release tablet. Experiments were performed on a water-soluble substance (thiamine nitrate) to characterize the effects of SLN upon the addition of the ALG coating formulation. The coated tablets or cast films were characterized based on delayed-release properties, surface morphology, moisture resistance, and chemical interactions. The SLN-ALG film displayed gastric-resistant properties (< 10% drug substance dissolved at pH 1.2) and rapid disintegration in the intestinal medium (pH 6.8). Morphological analysis using a microscope and scanning electron microscope confirmed the uniformity and smoothness of the SLN-ALG film, which improved the mechanical properties of the film. Fourier transform infrared spectroscopy and differential scanning calorimetry indicated that SLN contributed to the formation of the film, which maintained free carboxylic groups, making the SLN-ALG film a higher acid resistance, but soluble in pH 6.8 buffer. These promising results suggest a novel nanotechnology-based coating formulation for various enteric-release dosage forms. Because of their biodegradability, the proposed ingredients and processes are safe and environment-friendly.

\"Pulsed drug release\" for dosing drugs such as vaccines, hormones etc. that require multiple, predetermined release events can be obtained by using capsules that exploit the principle of osmosis to achieve a delayed burst release of their payload. An objective of this study was to precisely determine the lag time before burst which occurs when the hydrostatic pressure developed due to water influx expands the capsule shell to rupture. A novel \'dip coating\' technique was used to encapsulate osmotic agent solution or solid within biodegradable poly(lactic acid-co-glycolic) (PLGA) spherical capsule shells. As a prelude to determine the hydrostatic pressure to burst, first, elastoplastic and failure characterization of PLGA was conducted by a novel \"beach ball inflation\" technique. The lag time before burst of various capsule configurations was predetermined by modeling the rate of water uptake by the capsule core as a function of capsule shell thickness, radius of the sphere, core osmotic pressure, and the membrane\'s hydraulic permeability and tensile properties. In vitro release was studied with capsules of different configurations to determine their actual time to burst. The time to rupture predetermined from the mathematical model corroborated with the in vitro results and was found to increase with increases in capsule radius and shell thickness and decrease in osmotic pressure. Pulsatile drug delivery can be achieved by using a multitude of these osmotic capsules consolidated in a single system, each programmed to release the drug payload after a pre-determined time lag.

Intrinsically, enteric capsule shells offer several advantages compared to coating of dosage forms with enteric polymers. We undertook a systematic investigation to elucidate capsule-fill parameters that may result in premature gastric drug release from Vcaps® Enteric capsules (Lonza CHI, Morristown, NJ, USA). Four model drugs with different ionization and solubility profiles were investigated: acetaminophen, ketoprofen, trimethoprim and atenolol. Different fill loads, diluents and drug-to-diluent ratios were explored. Enteric capsules were filled with drug or drug and diluent powder mix and underwent USP II dissolution testing using mini-vessels and paddles. Capsules were tested in pH 2 (0.01 M HCl) or pH 4.5 (3.2 × 10-5 M HCl) 200 mL acid media to simulate normal, fasted or hypochlorhydric gastric pH, respectively. Acetaminophen, trimethoprim and atenolol displayed premature gastric drug release from enteric capsules. The extent of premature release was dependent on drug solubility, ionization profile and capsule-fill level. At 100 mg drug-fill level, acetaminophen, trimethoprim and atenolol gave rise to 10.6, 12.2 and 83.1% drug release, respectively, in normal, fasted, gastric fluids. Diffusion layer pH of trimethoprim and atenolol in pH 2 media was determined to be pH 6.3 and 10.3, respectively. Upon increasing capsule-fill load using microcrystalline cellulose as a diluent, a significant reduction in premature gastric release was observed. However, including mannitol as a diluent was only effective at decreasing premature drug release at a low drug-to-diluent ratio. Systematic in vitro screening of enteric capsule fills needs to be conducted to ensure that drug product performance is not compromised.

Most current animal vaccine regimes involve a primary vaccination followed sometime later by a booster vaccination. This presents challenges when vaccinating difficult to access animals such as livestock. Mustering livestock to deliver a vaccine boost is costly and stressful for animals. Thus, we have produced a platform system that can be administered at the same time as the priming immunisation and delivers payload after an appropriate delay time to boost the immune response, without need for further handling of animals. A 30 × 2 mm osmotically triggered polymer implant device with burst-release characteristics delivered the booster dose of a tetanus vaccine. Blood samples were collected from an experimental group that received the priming vaccine and implant on day 0 and control group that received the initial vaccine (tetanus toxoid) and then a bolus dose 28 days later via subcutaneous injection. The two groups showed identical weight gain curves. T cell proliferation following in vitro stimulation with antigen was identical between the two groups at all time points. However, serum IgG antibody responses to the tetanus toxoid antigen were significantly higher in the control group at weeks 8 and 12. The implant capsules stayed at the site of implantation and at week 12 there was evidence of tissue integration. No local reactions at the implant site were observed, other than mild thickening of the skin in half of the experimental group animals and no other adverse health events were recorded in either group.