Current progress of oral site-specific dosage forms: Emphasis on gastroretentive drug delivery systems

The oral route of administration is considered the easiest, most convenient, and most widely used drug delivery route. One of the hardest challenges facing oral drug delivery systems (DDS) is the erratic absorption of drugs through the gastrointestinal tract (GIT). The conventional oral dosage forms usually suffer from low bioavailability, especially in the case of drugs with narrow absorption windows (NAW). The oral controlled-release dosage forms could overcome the previous limitation by providing predicted and calculated drug release, resulting in an improvement of the efficacy of drugs. One of the most promising types of oral controlled-release dosage forms for this purpose is the gastro retentive drug delivery system (GRDDS), which was found to improve the gastric retention of the dosage form and maximize the absorption and bioavailability of the drugs with NAW. In this review, we summarize the different GRDDS techniques used for improving drug absorption, their methods of preparation, and their mechanisms of action.


INTRODUCTION
The oral route of administration is considered the most convenient route among other routes. It offers many advantages including the ability to offer immediate or controlled release. In addition,

Biological factors (gender and age)
It was reported that there is a significant decrease in GRT in males than in females.

Low-density/floating systems
The floating technique is one of the most promising techniques for the formulation of a GRDDS, which is widely used to prolong the GRT. It relies on the immediate floating of the dosage form owing to its low bulk density, which allows the dosage form to float for a long period over the gastric fluid until complete drug release occurs with a specific rate, as shown in Fig. 1.
The techniques used to decrease the bulk density of a dosage form depend on either creation of a hollow chamber through air entrapment or incorporation of low-density substance like oil or fat or foam powder [10,17]. According to the technique applied for the formulation, floating drug delivery systems (FDDS) are classified into two systems; effervescent systems and noneffervescent systems, as detailed below and displayed in Table 2.

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The results revealed that XG had the highest swelling ability.  The optimized formulation retarded the drug release and maintained floated up to 12h. [27]

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The results showed that HPMC was the polymer that gave the best buoyance behavior of tablets, while HPC alone did not achieve buoyancy.  The tablet buoyancy depended on formulating an HBS with a density less than gastric content by trapping the air within the swollen polymer and the release controlled by the diffusion of the drug from the boundary gel layer formed by hydration of the hydrocolloid polymer.  The in vivo study revealed significantly improved bioavailability after a single oral dose of selected formulations compared with conventional tablets of the same dose strength. [33]

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The formulations were prepared by applying the ionotropic gelation technique.  The optimized formulation was successfully prepared to retain the drug in the stomach, it showed entrapment efficiency of 96.23% and in-vitro drug release of 95.62% at 12 h. [37]

Floating micro balloons/ hollow microspheres
Lopinavir Eudragit S-100  The floating hollow micro balloons are prepared by the non-aqueous solvent evaporation method.  The selected formulation showed an entrapment efficiency of 91.82% and prolonged the drug release by about 86.35% at 12 h.

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The study formulated floating microspheres by emulsion solvent diffusion technique.

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The results showed that the optimized formulation had good encapsulation efficacy with favorable buoyancy and prolonged drug release accounting for 98% at 12 h. [42]

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The formulation was prepared by dispersion and homogenization techniques.

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The results showed that the increase in the quantity of both guar gum and GMS lead to an increase in the gelation duration and the release up to 24 h with a minimum floating lag time.

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In vivo pharmacokinetic studies showed that the prepared formulations exhibited greater AUCo-t, Cmax, t max , and t 1/2 when compared to the marketed formulation.

[45]
Bupropion Pectin and alginate as in-situ gel-forming polymer Sodium Citrate, The liberation of CO 2 upon contact of the formulation with acidic pH leads to the formation of an ionic intermolecular crosslinking between polymers and divalent ions resulting in the gels network causing the system to float and this caused a decrease in the density system.  The selected formulation showed excellent floating behavior with prolonged drug release reached 54.17% at 8 h and could control the release for more than 12 h.

Non-effervescent floating systems
The mechanism of a non-effervescent

High-Density systems
A high-density system relies on designing a dosage form with higher density than gastric fluid (A density close to 2.5 g cm -3 is considered optimal for significant prolongation of GRT  In their study, the drug was loaded onto a

Magnetic systems
In this system, a small internal magnet is incorporated in the dosage form along with a magnet that is positioned concomitantly over the stomach to retain the loaded drug in the stomach.
This system is not preferred as it has many drawbacks such as poor patient compliance and

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