Table 3.
Selected examples of single-unit low-density systems.
| Formulation | Matrix Forming Polymers | Drug | Other Components |
FT FLT |
Sustained Release (h) Drug Release (%) | Technique | Comments | Ref. |
|---|---|---|---|---|---|---|---|---|
| HBS Capsule |
HPMC K4M or PEO (60 K, or WSR 303, or WRS 301) |
Metformin hydrochloride | EC, CAP, LP | 12 h … |
7–12 h (97%) |
Physical blending | EC, CAP, LP: release modifiers.Best results: HPMC + EC. | [41] |
| HBS Capsules |
HPMC (Metolose 65SH) | L-DOPA | Carrageenan | 3–5 h 0 s |
3–5 h (≈48–100%) | Physical blending | Carrageenan promoted water uptake. | [43] |
| Tablets | HPMC K15M | Propranolol hydrochloride | NaCMC or Carbopol 934P **Citric acid and NaHCO3 |
2 h – >12 h 7–26 s |
>12 h (79–87%) | Direct compression | ≥27.5% of HPMC was needed to maintain matrix integrity. Ionic interaction of NaCMC with drug. Carbopol 934P reduced FLT in contrast with NaCMC. Effervescent. | [44] |
| Tablets | HPMC K15M | Venlafaxine hydrochloride | Hydrogenated cottonseed oil, Carnauba wax Cetyl alcohol *NaHCO3 | >24 h 24–104 s |
24 h (>95%) | Melt granulation and compression | Cottonseed oil, carnauba wax, cetyl alcohol: Hydrophobic meltable materials and behave as retardant agents. Effervescent. | [45] |
| Tablets | HPMC (METHOCEL™ K100LV, K100M, K15M) | Pregabalin | PVPP/Croscarmellose (Na) Cetyl alcohol/Glyceryl behenate MCC | 6.6 – >24 h 0.3–5.3 min |
24 h (≈100%) | Wet granulation and compaction | Cetyl alcohol/Glyceryl behenate: floating-assistance agents. PVPP/Croscarmellose sodium: swelling and disintegrating agents. | [46] |
| Bilayer Tablets | HPMC (K4M, K15M, K100 M) | Pioglitazone (PG) Metformin hydrochloride (MH) |
Layer of PG: NaCMC. Layer of MH: MCC, stearyl alcohol. *NaHCO3. |
24 h (in vitro) 5 min |
PG: 5 min (100%) MH: 12 h (> 95%) |
Wet granulation and compaction | NaCMC: disintegrant agent. Stearyl alcohol: floating-assistant agent. In vivo evaluation. Effervescent. | [47] |
| Tablets | HPMC K4M G43/01 | Famotidine | *NaHCO3 | 10 – >24 h 52 – >300 s |
8–12 h (80–100%) | Melt granulation and compression | G43/01: hydrophobic meltable binder. Effervescent. | [48] |
| Tablets | HPMC K4M Polyox WSR 303 | Baclofen | *NaHCO3 | >12 h (in vitro) 4–5 s >6 h (in vivo) |
12 h (in vitro) 2.34–2.43 times increase in bioavailability (in vivo) |
Direct compression | In vivo studies. Effervescent. | [49] |
| Tablets | HPMC (Methocel™ K4M, K15M, K100M) Polyox™ (WSR 1105)Xanthan gum |
Ofloxacin | **Citric acid and NaHCO3 | >24 h 20–200 s |
24 h (≈55–100%) | Direct compression | Polyox™ WSR 1105/Xanthan gum: gelling agents. Drug release rates retarded by HPMC with higher viscosities. Effervescent. | [50] |
| Tablets | HPMC (different viscosity grades)HPC (different viscosity grades)PEO WSR 303 |
Metformin hydrochloride | MCC *NaHCO3 | 24 h 1–60 s |
6–24 h (100%) | Direct compression | HPMC, HPC, PEO: hydrophilic gel-forming polymers. NaHCO3: gas forming /drug retardant agent. Effervescent. | [8] |
| Tablets | HPMC (intragranular) PVPP (extragranular) | Pregabalin | HPC (intragranular) PEO, MCC (extragranular) | >24 h 8–21 s |
24 h (≈75–100%) | Wet granulation and compaction | HPMC and PVPP were critical excipients in buoyancy and dissolution. HPMC, PVPP: release retardants. PVPP improved buoyancy. | [26] |
| Tablets | HPMC combined or not with a gum (Guar gum, Xanthan gum or Karaya gum) | Atorvastatin calcium | PVP (K-30) MCC | 6–12 h 6–20 min |
6–12 h (≈96%) | Direct compression | Combination of HPMC and guar gum enhanced bioavailability of the drug. | [51] |
| Tablets | HPMC K15M NaAlg | Ciprofloxacin hydrochloride | MCC *NaHCO3, CaCO3 | 8 – >12 h (in vitro) 8–165 s |
12 h (in vitro) (≈65–100%) | Direct compression | Floating and bioadhesive properties. NaAlg or HPMC: release retardant.NaAlg shortens FLT. CaCO3: gas forming agent and crosslinker. Effervescent. | [27] |
| Tablets | HPMC K4M NaAlg Carbomer 934P | Imatinib mesylate | MCC *NaHCO3 | 18 – >24 h (in vitro) 23–119 s |
24 h (≈44–76%) | Wet granulation and compaction | NaAlg, Carbomer: release retardant. In vivo studies (rabbits). Effervescent. | [52] |
| Tablets | HPMC Functionalized calcium carbonate (FCC) | Paracetamol | MCC, CaCO3, mannitol | … | … | Wet granulation and compaction | HPMC: binder for wet granulation. MCC, CaCO3, mannitol: for comparison on compactability with FCC-based tablets. FCC-based tablets with mechanical properties ≥ to those with MCC. | [53] |
| Coated Tablets | HPC (different viscosity grades) | Ofloxacin | MCC NaAlg (coating layer) *NaHCO3 (coating layer) |
> 12 h 15–38 s |
12 h (≈70–100%) | Wet granulation and compaction | Combination of HPC with different viscosity grades allowed to adjust FLT, FT and drug release. NaAlg behaved as a release retardant. Effervescent. | [54] |
| Tablets | HEC NaAlg | Pentoxifylline | MCC *NaHCO3 | > 24 h 26–55 s |
24 h (≈90–100%) | Wet granulation and compaction | HEC and NaAlg used as gel-forming polymers. Effervescent. | [55] |
| Tablets | HEC NaCMC | Losartan | *NaHCO3 | 16 h - >24 h 1–4.5 min |
24 h (≈30–80%) | Direct compression | HEC imparted enhanced floating capacity. Tablets with higher NaCMC content had longer FLT. Effervescent. | [56] |
*NaHCO3: gas forming agent, **Citric acid/NaHCO3: gas forming mixture. Abbreviations: CAP: Cellulose acetate phthalate; EC: Ehytl cellulose; FCC: Functionalized calcium carbonate; FLT: Floating lag time; FT: Floating time; G43/01: Gelucire® 43/01; HBS: Hydrodynamic balance system; HEC: Hydroxyethyl cellulose; HPC: Hydroxypropyl cellulose; HPMC: Hydroxypropylmethyl cellulose; LP: Liquid paraffin; MCC: Microcrystalline cellulose; MH: Metformin hydrochloride; NaAlg: Sodium alginate; NaCMC: Sodium carboxymethyl cellulose; MCC: Microcrystalline cellulose compression enhancer; PEO: Polyethylen oxide; PG: Pioglitazone hydrochloride; PVP: Polyvinyl pyrrolidone; PVPP: Polyvinylpolypyrrolidone (Crospovidone).