Enhanced Rectal Absorption of Sodium Ampicillin by N-Acyl Derivatives of Collagen Peptide in Rabbits and Rats

Yata, Noboru; Wu, Whei Mei; Yamajo, Ryoko; Murakami, Teruo; Higashi, Yasuhiko; Higuchi, Takeru

doi:10.1002/jps.2600741007

Cited by 13 publications

(1 citation statement)

References 27 publications

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“…A drug molecule with optimal structural configuration and physicochemical properties for eliciting the desired therapeutic response may not necessarily possess the best molecular framework and properties for its delivery at the target site. A therapeutically significant drug may have limited utilization in clinical practice because of various shortcomings [14] like poor organoleptic properties (chloramphenicol), poor bioavailability (ampicillin) [15], short duration of action (pilocarpine), and non specificity [16] incomplete absorption [17], poor aqueous solubility [18], high first pass metabolism (propranolol) or other adverse effect. Sometimes an adequate pharmaceutical formulation can overcome these drawbacks, but often the galenic formulation is inoperant and a chemical modification of active molecule is necessary to correct its pharmacokinetic insufficiencies.…”

Section: Introductionmentioning

confidence: 99%

Product Development Studies of Amino Acid Conjugate of Aceclofenac

Singh

Ramadan²,

Dahiya³

et al. 2009

CDD

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The prodrugs designed by classical approach increase lipophilicity of the drug, which decreases the water solubility thus decreasing the concentration gradient, which controls drug absorption. To overcome the limitations of traditional prodrug approach, water soluble prodrugs can be designed by adding selected amino acid to the drug moiety that are the substrates for the enzyme located at the intestinal brush border thus overcoming pharmaceutical problem without compromising bioavailability. ACaa (Amino acid conjugate of Aceclofenac) was synthesized by conjugation with l-phenylalanine by conventional coupling method using N, N-dicyclohexylcarbodiimide and ACaa was characterized by melting point, TLC, photomicrograph, UV, FT-IR, FT-NMR, MS-FAB, XRD and DSC. As a part of product development study ACaa was subjected to studies like In-vivo in albino rats and in-vitro like ACaa reversion to AC (Aceclofenac) in aqueous buffers of pH 1.21, 2.38. 3.10, 6.22 and 7.41, at a constant concentration (0.05M), ionic strength (micro = 0.5) and at a temperature of 37 degrees C +/- 0.5 degrees C, ACaa showed negligible reversion (2.15 %) up to 24 hrs study at acidic pH thus suggesting stability in acidic environment of stomach, the rate of reversion increased as pH of medium increased. pH- partition profile, pH- solubility profile and micromeritic studies were also carried out in comparison to pure drug. The solubility and lipophilicity of ACaa exhibited higher values at all pH range when compared to AC. The micromeritic properties also evaluated in terms of particle shape and size, IQCS and kurtosis. Resulting IQCS value approached zero thus suggesting reducing in the degree of skewness.

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Section: Introductionmentioning

confidence: 99%