Table 7.
Selected examples of multi-unit low-density systems.
| Formulation | Matrix Forming Polymers | Drug | Other Components | FT FLT |
Sustained Release (h) Drug Release (%) |
Technique | Comments | Ref. |
|---|---|---|---|---|---|---|---|---|
| CaAlg beadsand solid dispersion | NaAlg | Famotidine Quercetin (QRT) | Eudragit® RL100 PVP K30 *CaCl2 |
8 h 0 s |
In vivo studies |
Ionotropic gelation method | Eudragit® RL100: for coating formation. PVP: to form solid dispersion of QRT. |
[122] |
| Coated chitosan alginate beads | NaAlg Chitosan |
Ranitidine hydrochloride | *CaCl2 CaAlg, PVA |
72 h 0 s |
11 h 100% |
Ionotropic gelation method | With air compartment. CaAlg, PVA: formation of semipermeable coating. |
[30] |
| Inner porous beads | NaAlg Poloxamer 188 |
Riboflavin | *CaCl2 | 6 h 0 s |
10 h ≈65–85% |
Ionotropic gelation method | Poloxamer 188: foaming agent. | [37] |
| CaAlg beads | NaAlg | Ibuprofen | MS LP *CaCl2 |
8 4.5 min |
8 h 35% |
Ionotropic gelation method | MS and LP: floating-assistance and release retardant agents. | [36] |
| Coated oil-entrapped Alginate beads | NaAlg Sterculia gum |
Risperidone | Olive oil *CaCl2 |
8 h 3–6 min |
8 h 64–83% |
Ionotropic gelation method | Floating and mucoadhesive beads. | [35] |
| Coated oil-entrapped Alginate beads | NaAlg HPMC |
Amoxicillin | Chitosan Sunflower oil *CaCl2 |
24 h 46 s |
In vivo studies |
Ionotropic gelation method | Floating and mucoadhesive beads Chitosan: coating polymer. | [3] |
| Hollow CaAlg beads | NaAlg Carrageenan |
Brucea javanica oil | *CaCO3 *CaCl2 |
24 h 0 s |
… | Ionotropic gelation method | Carrageenan: porogen. CaCO3: release of Ca ion crosslinker and gas forming agent. Effervescent. |
[123] |
| Calcium pectinate beads | LM Pectin HPMC K15M Carbopol® 934P Polycarbophil |
Famotidine | Cod liver oil *CaCl2 |
24 h 0 s |
8 h (80%) Biphasic release |
Emulsion gelation | Cod liver oil: floating-assistance agent (20% was necessary). Other polymers behave as release retardant. |
[124] |
| Zinc pectinate Beads | LM Pectin | Ofloxacin | Gellan Gum, Karaya Gum, Xanthan Gum Rice bran oilZnCl2 |
24 h 0 s |
8 h 60–88% |
Ionotropic gelation method | Gellan Gum, Karaya Gum, Xanthan Gum: Release retardants. Rice bran oil: floating-assistance agent. Zinc ions: crosslinker. |
[125] |
| Coated CaAlg beads | NaAlg Gelatin Pectin HPMC |
Gliclazide | *CaCO3 *CaCl2 |
10 h … |
10 h At pH 1.2: 33–46% At pH 5.8: 82–95% |
Ionotropic gelation method | CaCO3: release of Ca ion crosslinker and gas forming agent. Effervescent. |
[126,127] |
| Minitablets (MT) | G43/01, G39/01 |
Nimodipine | COM PRE |
14 h<1 min | 12 h (95%) |
Melt granulation and compression | COM: blend of esters of behenic acid with glycerol. PRE: glyceryl palmitostearate COM, PRE, G39/01, G43/01: release retardants. |
[113] |
| Porous beads | Eudragit® L | Metronidazole | Cetyl alcohol | >8 h 0 s |
8 h >90% |
Solvent evaporation and extrusion | Cetyl alcohol: floating-assistance agent, porogen, and release retardant. Solvent: acetone and extruded into DCM. |
[128] |
| Lipid-based beads | G43/01 G50/13 |
Cinnarizine | Sterotex® Pluronic® F-127 |
>24 h 0 s |
8 h (≈45–95%) |
Hot melt method | Sterotex®: Hydrogenated cotton seed oil. Pluronic® F-127 enhanced drug release. |
[118] |
| Lipid-based pellets | HPMC K4M G44/14 G50/13 |
Berberinehydrochloride (BERH) | G43/01 COM MCC NaHCO3 |
5–9 h 0 s |
8 h (70–99%) |
Hot melt method | COM, G43/01: release retardants. MCC: spheronizing aid. NaHCO3: gas generating agentEffervescent. |
[114] |
| Granules | HPC G50/13 |
Metronidazole | COM NaHCO3, citric acid PEG 8000 |
8–0 0 h≈40–100% … |
>10 h (>60%) |
Fluidized hot melt granulation | COM, G50/13: meltable binders. PEG 8000: release enhancer. G50/13 and HPC increased drug release. Citric acid + NaHCO3: gas generating mixture. Effervescent. |
[120] |
| Granules | G43/01 | Torsemide | … | 8 h 0 s |
8 h (86%) |
Melt granulation | Lipid carrier: G43/01. | [115] |
| Microspheres | EC | Ranitidine hydrochloride | PEG 4000 | 4–10 h 5–10 min |
4–6 h (85–100%) |
Solvent evaporation- matrix erosion method | PEG: pore forming agent. PEG (20–33%) induced buoyancy. Reduction in size at higher PEG content. |
[129] |
| Bioadhesive Microspheres | NaAlg | Acyclovir | LP Technetium-99m SnCl2, CaCl2 |
>4 h (in vivo) … |
8 h (in vitro) (40–72%) |
Emulsification phase separation method | Mucoadhesive properties. In vivo studies. (Radio-labeled microspheres). Higher sizes at high polymer conc. Ca ions: crosslinker. |
[130] |
| Microspheres | Eudragit® S-100 | Famotidine | PVA | 20 h 0 s |
4–20 h ≈85–100% |
Solvent evaporation method | Formation of O/W emulsion. PVA: emulgent. Porous formed by solvent evaporation (DCM). |
[130] |
| Microspheres | CTS | Itraconazole | MβCD, PEG TPP DOS |
12 h (in vitro) 6.5 h (in vivo) |
8–12 h<40 mg of drug | Ionotropic gelation method | MβCD, PEG: drug solubilizing agents. DOS, TPP: crosslinking agents. Drug release decreased with higher CTS concentration. |
[131] |
| Multiparticulates | For MH: G39/01, G43/01 For GLB: G50/13 + PEG |
Metformin hydrochloride (MH) Glibenclamide (GLB) |
For MH: EC, MC, MCC For GLB: … |
MH: 10–12 h GLB: 7–11 h … |
MH: 8 h (80%) GLB: 3 h (80%) |
Hot melt method | G50/13: good carrier for fast release.EC, MC, MCC: granulating agents. |
[116] |
| Microparticles | HPMC (various grades)Eudragits® S100, L100, 100-55 |
Risperidone | G43/01, G44/14, G50/13 COM, GMS, Geleol mono and diglyceride MβCD, HPβCD |
12 h … |
12 h (71–93%) |
Emulsion solvent diffusion technique | Lipid carriers: GMS; Geleol mono and diglyceride; G43/01, COM. MβCD, HPβCD: drug solubility and stability enhancers. Best polymers: Eudragit® S100, HPMC E50. |
[117] |
*Ca ions: crosslinker. Abbreviations: CaAlg: Calcium Alginate; CNZ: Cinnarizine; COM: Compritol 888 ATO; CTS: Chitosan; DCM: Dichloromethane; DOS: Dioctyl sodium sulfosuccinate; EC: Ehytl cellulose; FLT: Floating lag time; FT: Floating time; G39/01: Gelucire® 39/01; G43/01: Gelucire® 43/01; G44/14: Gelucire® 44/14; G50/13: Gelucire® 50/13; GLB: Glibenclamide; GMS: glyceryl monostearate; HPC: Hydroxypropyl cellulose; HPMC: Hydroxypropylmethyl cellulose; HPβCD: Hydroxypropyl-betacyclodextrin; LP: Liquid paraffin; LMP: Low methoxylated pectin; MβCD: Methyl-betacyclodextrin; MC: Methyl cellulose; MCC: Microcrystalline cellulose; MH: Metformin hydrochloride; MT: Minitablets; NaAlg: Sodium alginate; PEG: Polyethylene glycol; PRE: Precirol ATO05; PVA: Polyvinyl alcohol; PVP: Polyvinyl pyrrolidone; TPP: Sodium tripolyphosphate.