A Novel Drug Delivery System: Floating Microspheres in the Development of Gastroretentive Drug Delivery System

Gastric emptying is a complicated process in the human body because it is very inconstant, resulting in ambiguous in vivo drug delivery system efficacy. To combat this variability, scientists have been working on developing a regulated medication delivery system with a long gastric residence period. This review article on gastroretentive drug delivery systems (GRDDS) focuses on numerous gastroretentive approaches that have recently emerged as a leading methodology in the field of site-specific orally administered controlled release drug administration. Gastroretentive medicines come in a variety of forms on the market, including tablets, granules, capsules, floating microspheres, laminated films, and powders. Floating microspheres are currently garnering more attention than previous techniques because of their benefits, which include more consistent drug absorption and a lower risk of local discomfort. The primary goal of this method is to increase gastric retention time in the GIT, which is defined as more than 12 hours in the stomach with an absorption window in the upper small intestine. Longer stomach retention improves bioavailability, reduces drug waste, and boosts solubility for medications that are less soluble in a high pH environment. The medicines are released into the stomach for a long time and consistently thanks to the floating microsphere systems. The current study compiles the most recent research on the techniques of production, characterization, and numerous aspects that impact the performance of floating microspheres for oral administration.

A Review on Gastro-Retentive Floating Microspheres

The floating microsphere's purpose is to improve gastric retention time. Floating drug delivery systems are lower in bulk thickness than gastric juice and remain floating on gastric juice for a long period of time without impacting the gastric-emptying rate and increasing bioavailability. Gastro-retentive microspheres are particularly suitable for the continuous or late release of oral formulations with blending versatility to achieve various release patterns, low dose risk as a reproducible and short gastric retention time. The aim of this review is to address literature on the floating device, techniques, selection of suitable or inappropriate drug candidates for GRDDS, low density polymers used to swim over gastric fluid, processes, and floating microsphere assessment and application. Keywords: GRDDS, Floating system, Approaches, Polymer, Mechanism, Methods

Formulation and optimization of gastroretentive bilayer tablets of calcium carbonate using D-optimal mixture design

Gastroretentive bilayer tablets of calcium carbonate (CC) were developed using D-optimal mixture design. The effect of formulation factors such as levels of HPMC K100 M (X1), sodium bicarbonate (X2), and HPMC E15 LV (X3) on responses like floating lag time (R1) and release of CC at 1 h (R2) and 6 h (R3) was elucidated. The optimized formulations developed by numerical optimization technique were found to have short floating lag time (2.85 ± 0.98 min), minimum burst release (27.02 ± 1.18%), and controlled yet near complete release (88.98 ± 2.75%) at 6 h. In vivo radiographic studies in rabbits indicated that optimized batch displayed a mean gastric retention time (GRT) of 5.5 ± 1 h which was significantly prolonged (P < 0.05) compared to the conventional tablets that displayed a GRT of less than 1 h. The studies proved that the gastroretentive tablets can be a promising platform to improve bioavailability of nutrients having absorption window in upper gastrointestinal tract.

Transglycosylated starch accelerated intestinal transit and enhanced bacterial fermentation in the large intestine using a pig model

Resistant starch can alter the intestinal nutrient availability and bulk of digesta, thereby modulating the substrate available for microbial metabolic activity along the gastrointestinal tract. This study elucidated the effect of transglycosylated starch (TGS) on the retention of digesta in the upper digestive tract, ileal flow and hindgut disappearance of nutrients, and subsequent bacterial profiles in pigs. Fourteen ileal-cannulated growing pigs were fed either the TGS or control (CON) diet in a complete crossover design. Each period consisted of a 10-d adaptation to the diets, followed by 3-d collection of faeces and ileal digesta. Consumption of TGS decreased the retention of digesta in the stomach and small intestine, and increased ileal DM, starch, Ca and P flow, leading to enhanced starch fermentation in the hindgut compared with CON-fed pigs. TGS increased ileal and faecal total SCFA, especially ileal and faecal acetate and faecal butyrate. Gastric retention time positively correlated toKlebsiella, which benefitted together withSelenomonas,Lactobacillus,Mitsuokellaand Coriobacteriaceae from TGS feeding and ileal starch flow. Similar relationships existed in faeces with Coriobacteriaceae, Veillonellaceae andMegasphaerabenefitting most, either directly or indirectly via cross-feeding, from TGS residuals in faeces. TGS, in turn, depressed genera within Ruminococcaceae,Clostridialesand Christensenellaceae compared with the CON diet. The present results demonstrated distinct ileal and faecal bacterial community and metabolite profiles in CON- and TGS-fed pigs, which were modulated by the type of starch, intestinal substrate flow and retention of digesta in the upper digestive tract.

A REVIEW ON FLOATING MICROSPHERES

The purpose of writing this review on floating microspheres is to compile the recent literature with special focus on the principle mechanism of floatation to achieve gastric retention. Recent advances indicate that floating microspheres are especially suitable for achieving sustained or delayed release oral formulations with flexibility of blending to attain different release patterns, low risk of dose dumping as well as reproducible and short gastric retention time. One of the approaches toward this goal is to develop the floating microspheres so as to increase the gastric retention time. In this review, the current status of floating microspheres including hollow microspheres (micro balloons) and their characterization, advantages, disadvantages, mechanism and method of preparation for gastric retention of drug are discussed. This review also summarizes the in-vitro dissolution study to evaluate the performance and applications of floating microspheres. Keywords: Floating microspheres, Floating Drug Delivery System, Gastro Retention, Bioavailability, Hydro dynamically Balanced Systems.

A REVIEW ON MICRO-BALLOONS

Oral prolonged release systems are manufactured to release the drug in-vivo with privies to enhance bioavailability, diminish untoward effectsand enhance effectiveness of drugs. Microballoons or hollow microspheres are anticipated to persist buoyant in a permanent way upon the gastricingredients. The various formulations comprise unfilled microspheres, powders, capsules, tablets and laminated films. Micro-balloons aredistinctly attaining attention due to their immense significance in the drug targeting to the stomach. These floating micro-balloons have theconvenience that they stay buoyant and circulate uniformly over the gastric ingredients to refrain the variations of gastric emptying and releasethe drug for extended period of time. Multiparticulate particles of low density can efficiently prolong the gastric retention time of drugs. Thisarticle provides an insight of fabrication and methods of evaluation of micro-balloons.

Drug-Excipient Interaction during Formulation Development, in vitro andin vivo Evaluation of Gastroretentive Drug Delivery System for Nizatidine

The present investigation dealswith the development and evaluation of floating tablets of nizatidine to prolong the gastric residence time, increase local delivery of drug to the H2-receptor of the parietal cell wall to reduce stomach acid secretion. The drug-excipient compatibility studies were conducted by using FTIR, DSC and visual observations. Citric acid inclusion in formulations resulted in incompatibility and the composition was modified to eliminate the problem of incompatibility. Floating matrix tablets of nizatidine were developed by direct compression method using hydroxypropyl methylcellulose (HPMC K4M) and polyox WSR 1105 alone as release retardants and sodium bicarbonate as a gas-generating agent. Alleleven formulations exhibited satisfactory physicochemical characteristics andin vitro buoyancy. Formulations F6 and F10 exhibited controlled and prolonged drug release for 10 h with zero order release. Formulation (F10) was selected as optimized formulation based on physicochemical properties and in vitro drug release and was used inradiographic studies by incorporating BaSO4. The radiographic studies were conducted in comparison with plain controlled release tablets. These studies revealed that gastric retention time of floating and plain controlled release tablets in fasting state were 2 ± 0.86 h and ≤ 0.5 h respectively in human volunteers. Gastric retention time of floating and plain controlled release tablets in fed state were 5.33 ± 0.57 h and 1.66 ± 0.28 h respectively in human volunteers. In conclusion, optimal floating matrix tablet for nizatidine with desired in vitro buoyancy, in vivo gastric retention time and prolonged release could be prepare